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·THE BIOLOGY OF AGEING

·Symposia of the Institute of Biology
BIOLOGICAL HAZARDS OF ATOMIC ENERGY
Oxford University Press, 1952
FREEZING AND DRYING
Institute of Biology 1952
THIE BIOLOGY OF DESERTS
Institute of Biology 1954
THE NUMBERS OF MAN AND ANIMALS
Oliver and Boyd 1955
BIOLOGICAL ASPECTS OF THE TRANSMISSION OF DISEASE
Oliver and Boyd 1957

·THE BIOLOGY OF AGEING
Symposia of the Institute of Biology, No. 6
EDITED BY
W. B. YAPP
and
G. H. BOURNE
LONDON
The Institute of Biology
41 Queen's Gate, S.W. 7
1957

·Symposia of the Institute of Biology
BIOLOGICAL ILAZARDS OF ATOMIC ENERGY
Oxford University Press. 1952
FREEZING AND DRYING
Institute of Biology 1952
THE DIOLOGY OF DESERTS
Institute of Biology 1954
THE NUMBERS OF MAN AND ANIMALS
Oliver and Boyd 1955
BIOLOGICAL ASPECTS OR THE TRANSMISSION OF DISCASA
Oliver and Boyd 1957

·I A FOREWORD The Institute of Biology has from time to time organized symposia, and the papers read at five of these have now been published. The hoor Amewhat broader than those which ied journals, peakers who I HA 159... ooked on as to make it difficult for ies, and the five that have in the shelves. It would imposia were brought towhat sometimes needs спрыяды, алы, мы cipline which can help in understanding many aspects in the life of man. The Council of the Institute has accordingly decided that the symposia shall take the form of a journal, with the volumes to appear as far as possible annually. The Biology of Ageing, the volume for 1957, becomes 1....lar of the river volumes are set out on p. ii. V e d have delayed publication unduly. W. B. YAPP, Editor for Symposia. ACKNOWLEDGEMENTS This volume is a record of the Symposium held at University ... 17. c.-amhe- 1046 We thank : Professor W.J. E. Jessop); University College, London, for the use of the lecture theatre; and the Nulield Foundation for a grant which enabled the parets to be printed and circulated before the mecting y ·durch Army Press, Cooley, Oilard, Cagland 313 ·.. 1 ... ... ... . O. CONTENTS Page ... IX Introduction By F. LE GROS CLARK and N. W. PIRIE Agcing in Dacteria .. By Prof, Sir Cyril HIMSHIELWOOD, P.R.S. Ageing in Higher Plants ... . .. 9 By Dr. O. V. S. HEATI! Agcing in Animals .. .. 23 By DR. ALEX COMFORT Ageing and Metabolism ... 27 By Prof. F. BOURLIÈRE The Ageing of Mammalian Cells .. 35 By Dr. G. H, BOURNE Some Endocrine Aspects of Ageing 47 By Dr. G.I. M. SWYER Demographic Aspects of Ageing 55 Tly Dr. B BENJAMIN Functional Changes with Age in Relation to the Employment 73 By Prof. W. HOBSON The Working Life as a Measure of Ageing in Men and Animals 81 By T. LE GROS CLARK Psychological Changes with Age 91 lly D: ALASTAIR HIROV Nutrition and Ageing 101 By Dr. 11. M. SINCLAIR Gencric Vanations in Agcing ... JJ5 By J. MASYARD SUMI Author Indet 125 Subject Index 127 ... of the Elderly 9. ... ... ... .. .. . .

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·.. ... ... 1 .. . . CONTENTS Page ... IX Introduction By F. LE GROS CLARK and N. W. PIRIE ... Ageing in Bactena By Prof. Sur CYRIL HINSIELWOOD, P.R.S. ... 9 Ageing in Higher Plants ... By Dr. O. V. S. HEATH Ageing in Animals 23 By DR. ALEX COMFORT Ageing and Metabolism 27 By Prof. F. BOURLIÈRE The Ageing of Mammalian Cells 35 By Dr. G. H. BOURNE Some Endocrine Aspects of Ageing ... 47 By Dr. G.I. M SWYER Demographic Aspects of Ageing ... 55 By Dr. B BENJAMIN Functional Changes with Age in Relation to the Employment of the Elderly 73 By Prof. W HOBSON The Working Life as a Measure of Ageing in Men and Animals 81 By F LE GROS CLARK Psychological Changes with Age ... 91 By Dr. ALASTAIR HERON Nutrition and Ageing ... .. 101 By DR. H. M. SINCLAIR Genetic Variations in Ageing ... .. 115 By J. MAYNARD SMITH Author Index 125 Subject Index 127 vii .. +

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·INTRODUCTION By F. LE GROS CLARK AND N. W. PIRIE A SYMPOSIUM on ageing needs some introduction. The subject has about it a deceptive simplicity, but that is partly because we have tended to assume that ageing as we know it in man must in some way characterize any plant or animal that has lived long enough. Only of late years has the subject received much attention from research departments-and that for reasons that are all too human Societies, such as our own, that contain a steadily increasing number of pensioners, were bound to grow more interested in the nature of Amin -- -- -- -- --L. delayed. answers, 1 probably inherent in the subject itself; senescence primanly means and always has meant human senescence, and human senescence is a A.128.-J. 10 11. A whissent should be added on the terminology of the subject. The contributors to the suminneum have hear ------ in their usage, but the used, and they appear to do we mean by the word It almost invariably sug. more precise bialnosti. Sequence of char of an organism, interpretation the process of be the layman, and implied a fixed st Before the biolog Th וגם th A. mius dy at any time prove lethal. Ageing must mean that organisms (though perhaps not all organisms) come to experience in the course of time a gradually increasmg ·Introduction liability to die, and often therefore to dic from causes that might formerly have left them more an laen. ages in this sense does viability until it has lit may recognize or think we recognize such a senescent process at work in the members of many species of animals, lc must not take for granted that the same deteriorative factors are at work in all of them. Indeed, to look for a cause of agcing common to all living things may be quite abortive. For one thing, it seems very probable that many organisms cannot be described as ageing at all Whicre ageing docs occur in living things it should perhaps be treated, as Dr. Comfort has suggested, rather as a unity of cflects than as a unity of causes. The factors that are operating may turn out to be too complex and too varicd to allow of any ncat biological classific.l. tion. The determination of the vulnerability of the members of an animal or plant population, with the passage of time, would be onc way of measuring and comparing types of ageing All we should need to know would be the chronological ages of all the individuals at risk within our sample. They have, of course, to succumb beforc wc know whicther and at what ralc thcir chances of dying have in. crcased with their chronological ages. It has been more robustly suggested in the symposium that another method of tracing deteriortic changes could be adopied--that of measuring the worling vigour of men and of some of their domesticated animals against the demands of fairly constant day-to-day tasks. If life tables can be constructed, why not working-lifc tables"? The time of fifc at which working men or draught animals can no longer carry out har inrich . calculation based on mortality rates A common-scnsc objection to measuring the degree of ageing in cither of these ways is that they would often gnca minimum not at birth but at some later acc. For man, for birds and for many other animals the chances of dying are high in carly life, and then fall to a minimum in what, in human tcrms, may be called late adolescence. There would be a similar, though less precise, marimum cipectation of working life It is a matter for discussion and research to decide whether these facts would constitute a biological objection to a definition of ageing made in this way. Since there is a distinctly human quality in the common ideas wc have about senescence, several of the contributions to the symposium wcrc confined to human aspects of thic problem It would indeeu te difficult to discuss the papers as a whole without making continua) reference to the human implications of the subject. The contribu. tions proude us with a brief suricy of the biological probiem of

·Introduction
xi
ageing, as it is at present understood. Obviously what the writers
has, one might say, no more permanence than the vortex in an
endlessly emptying bath that is being as endlessly replenished He
interprets ageing in such an organism as a failure to make the
absorption and retention of metabolites keep pace with losses due to
leakage. the deficiency could occur either through a reduced
absorption or through an increased leakiness. In the long run
failures of this kind would make a cell unworkable, and he prefers
1.
wwUswu wy Usejers with crick mannen
Howering
which il
festatior
here inc
writers
phuloso
--Audi Tianfestations promote
ageing or inevitably precede its onset.
This assumption runs
tlurough much of mediaeval and Calvinist thinking; and with Donne
it even reached the dignity of poetry:
"Since each such act they say
Dirtunisheth the length of life a day,"
ELIMU

·Introduction Apparently this belief in the ser.influenced contraction of life, whether plant or human, was based less on any moral principle than on the idea that an organism must at last run through its allotted reserves of energy or lose the structural capacity for dealing with the energy it so gloriously ctpends. The idea that an organism les till it has metabolized a definite amount of bodily cncrgy is only a more generalized version of the same theme. Rubner, for instance, once surmised that the amount would ordinarily be about 200,000 kilocalorics for every kilogram of an animal's adult body scight: he placed man in the crccptional position of being able to metabolize about four times as much as this. If that were so man's place in nature would take some explaining. But Professor Bourlidre shows below that things are not quite as simple as this, and that scvcral other animals are also exceptional. It may be truc that the "ratc of living" of a species docs in some way determine its a crage span "Y". alindinn ly reduce their · non-hubcrna. :. 'cing used up st know that 's of Icthargy that live longest; but it may be quite unjustifiable to compare them with bats. Dr. Bournc rcierts to the problem of the agcing of cells, this time as studied histologically within a multicellular organism. Ilc describes changes in the mitochondria of cells, which in the main seem to result in an increased fragility; the cell, like the whoic organism, finds, as it were, that its parts break morc casily and repair less easily as it grows chronologically older. There arc also more clearly definable changes going on within it, such as the accumulation of calcium, iron and pigments, and a variation in the concentrations of many of thc cnzymes. The cffects of ageing in an animal's tissues womandaly studied hemuise in many tissues the individual cells. onstantly tencued. But in tissues this kind there is a stcady loss of cells, and this is perhaps most cicarly seen in the central nervous system. Old age may, in fact, be due to an ultimately suicidat -- :!" organisms thc process of agcing could thus be reduced to a dugic uniform causal sequence of events. Cellular changes of this kind people the most crasperating feature of old age is apt to 'lue ut of sexual capacity and enthusiasm, there is a tendency to overlook the fact that cunuchs often inelo a ripe old age. Thic eunuch Nana ·Introduction xiii was well beyond seventy when he won his final battle against the Goths, and almost ninety before he was retired from the governorship of Italy. Dr Swyer surveys our knowledge of the changes in . preventing or counteracting some at least of the symptoms of advanced senescence. It is much to be hoped that this line of maennush «'11 duit --- ............ though they tend to live longer than men, appear to suffer more from the disabilities that might well be remediable by this type of replacement therapy The notion that certain properties in a man's diet could conceivably nrolono his life or inaue io nn Innen- !! I. Apr abc Scle tio -- veci desi MI ·xiv Introduction Dr. Comfort's paper on ageing in animals leads naturally to man. The impression charc of ageing in the animals with which we are most familiar is much the same as the impression of ageing as it is crperienced by the members of our own species. Whether the complex of causes is invariably the same is another matter. We shall plainly not get much further until wc possess detailed life tables for a number of species. It has been suggested in the course of the Symposium that comparative information might be obtained by obscrvatiors tha. -1:-." and clepha late in indt use of the Burma torcst clephant as a laboratory animal in the study of ageing offers some exciting prospects. In his survey of the clinical aspects of senescence Professor Hobson brings into relief the fact that old age is frequently accom. panicd by chronic diseases and ailments of one kind or another. Dr. Hcron emphasizes that in man at all events age is complicated by many, psychological changes. Mr. Benjamin completes the human picture by displaying the 1351 and shifting demographic framework within which ihe drama of ageing is now being played out in our own country. Our approach to the problems of scnescence must necessarily be in some measure subjective, as indeed are the conceptions we tend to adopt about our own place in society when we arrive at a chronologically advanced age. How subjective our approach is, we can scarcely rcalize, so ingrained have become our traditional habits of thought. Most of us ha cour words and gestures perfect as uc live through the Shakespearean Scvon Ages of Man. Yet a biological residuc remains which is clearly entitled to be called organic ageing. What precisely accumulates or breaks down or fails to function or runs out or goes to seed, we do not know, and it may be that none of thesc mctaphors is strictly applicable. We do not know whether we shall later find ourselves describing these experiences in neurological or biochemical or cytological terms; the chances are that no one of the biological sciences will alone prove adequate to our purpose.

·AGEING IN BACTERIA Ву C. N. HINSHELWOOD Physical Chemistry Laboratory, University of Oxford number of cells, and the masses of the various components, all increase according to an exponential law, and with the same rate constant for each. n, ne", (m): = (m.).et and so on. The steady rhythm of growth and reproduction is seldom maintained for long, and indeed with cells such as bactena, can only continue under rather carefully devised laboratory conditions. If one or other pront.nl want hanamar where .. phase of exponential increase is upset. To understand the ways in which it is disturbed some attention must first be given to the kind of harmony which had been established during the preceding steady state. mann Vi unui syutuses there must be many sequences of consecutive reactions. These sequences must branch and interlock in a complicated scheme which constitutes the reaction pattern of the cell. It is very unlikely indeed that there are individual substances capable of autosynthesis in isolation and in their own right. The process of self-duplication is much more probably the result of a co-ordinated interplay of reactions in which the products of one set of enzymes or cell constituents build up the material of another, ·xiy Introduction Dr. Comfort's paper on ageing in animals leads naturally to man. The impression we have of ageing in the animals with which we are most familiar is much the same as the impression of ageing as it is experienced by the members of our own species. Whether the complex of causes is invariably the same is another matter. We shall plainiy not get much further until we possess detailed life tables for a number of species. It has been suggested in the course of the symposium that comparative information might be obtained by observations on the working lives of such draught animals as horses and elephants, but doubt is expressed whether we have not come too late in industrial history to hope for reliable records The possible use of the Burma forest elephant as a laboratory animal in the study of ageing offers some exciting prospects. In his survey of the clinical aspects of senescence Professor Hobson brings into relief the fact that old age is frequently accompanied by chronic diseases and ailments of one kind or another. Dr. Heron emphasizes that in man at all events age is complicated Mr. Benjamin completes the .. vast and shifting demographic of ageing is now being played out in our own country. Our approach to the problems of senescence must necessarily be in some measure subjective, as indeed are the conceptions we tend to adopt about our own place in society when we arrive at a chronologically advanced age. How subjective our approach is, we can scarcely realize, so ingrained have become our traditional habits of thought. Most of us have our words and gestures perfect as we live through the Shakespearean Seven Ages of Man. Yet a biological residue remains which is clearly entitled to be called organic ageing. What precisely accumulates or breaks down or fails to function or k... or biochemical or cytological terms; the chances are that no one of the biological sciences will alone prove adequate to our purpose.

·Ageing in Bacteria 3 processes which cause serious departures from the steady state set disturbance has been. Furman af en Talely co-ordinated activities, The breakdown of glucose and other carbon compounds, so fundamental for the complete process of growth and multiplication. can of course be observed with suspensions of bacteria which are prevented from growing by the absence of any nitrogen source. The use of radioactive tracers shows tbat in the early stappe of shie . vuld cuilures can be prepared by growth in media containing radioactive sulphur, phosphorus or carbon The cells containing this labelled material can then be suspended ja a medium lacking one of the essential components for growth, and as they sojourn here any exchange with the medium can be followed. In these circumstances what is observert is classe artita al integratior verted, pilu (be active elements added to the external medium. 2 expennents can be in- ·2 Hinshelwood and so on in an interlocking system according to cquations of the type dX/d=aX, dX,/di=a, X, and so on. It is casy to show that in the steady state of such a system dX;/di= kX1, dX,/di=kX, and so on, all the k's being cqual, and the ratios X1/X3, X1/X3 .. "' values. These ratios are maintai gocs on in a constant medium. new medium where the relative rates of different individual reaction stcps of the complex rcaction pattern are changed, the cell automatically undergoes an adaptive modulation to a new set of ratios. When the maintenance of the complete rhythm is interrupted by the failure of supplies, there is no necessity at all for all the individual reaction steps to cease simultancously and they do not do so. After the fully co-ordinated working (which leads to increase in size followed period division) has been upset many different things may happen to bacterial cells. In some circumstances division may.continuc without increase in the tot When ехатр. Thus morc is synthesized from somewhere. The necessary phosphorus has been shown in certain cxamples to be derived from the ribose nucleic acid aircady formed. Direct interconversion of ribose nucleic acid and dcoxyribosc nucleic acid being unlikely in the circumstances, a reversal of the condensation processes by which the ribose nucleic acid was originally formed scems to be involved, 1. uscd, for ibly after In other shown to increase at the end of the lag phase to a steady level which is reached at the expense of inorganic phosphate in the medium and which is maintained during the logarithmic period. The level falls again as w C been in balance continue in a less co-ordinated way. Even more significantly thcy indicate how certain synthetic processes (c.g. the deoxyribosc nucleic acid formation) can occur by a re-allocation of the internal resources of the cell, made possible by a reversal of previous syntheses. This principlc will prove of importance in what follows. The consumption of labile intermediates, the re-distribution of material by degradation and fresh synthesis, the decay of cnzymc systems, and sometimes actual lysis of parts of the cell. arc all ·Ageing in Bacteria $ substances. The exponential law is by no means exactly followed. Sometimes there is an initial period during which the death rate is quite low and it rises only after the adverse environment has had time to bring about progressive changes in the cells. Sometimes, on the other hand, there is a resistant tail of cells which survive much longer than the simple law would predict. But the exponential curve is often enough followed sufficiently closely for it to possess theoretical significance. At its face value such a law imples that the chance of death in a given short time interval for any cell is independent of its previous history, as in the well known phenomenon of the radioactive decay of atoms. The interpretation given in the well known" target" thcory is that some sensitive centre in the cell receives a random hit from a molecule of a toxic agent, or from a quantum of high energy radi- --.L & L...-1.1-1 TE that adequate experimental technique would reveal an early region of the decay curve where the chance of death increases with time, as is required by theories that the toxic agents cause progressive damage. Nevertheless, there is no drht that the is sometimes r pretation of it to the theory economy of a i fectly co-ordina explanation In onc cance thans in to unrave . unidirecti actual ly... I LULULIZOU pasis of the material may set in, poly. merization and condensation reactions may be reversed. But as some of these things happen, the internal medium of the cell is enriched by compounds containing carbon, futrogen and other elements which can be used for the renais new -0.1 combated the coordi the constiti ·4 Hinshelwood Little actual uptake of the labelled elements is then observed. What occurs is thus predominantly a slow one-way leakage but one which involves essentially the living cells. The explanation seems to be as follows. There is a lively internal interchange of materials within the living, but non-dividing cell, compounds formed by reversed synthesis in one part being more or less avidly salved for re-synthesis in another (as in the example of the RNA DNA conversion). The salvage mechanism is, however, not perfectly eſlicient and some of the intermediates leak slowly out. The time scale of the leakage is such that the experiments extend over a period which may vary from several days to several weeks. Since radioactive markers began to be available for the investigation of the detailed balance sheet of reactions in cells and tissues, permanence, are dissolved and renewed according to a timc scale of days or weeks. It is true that this almost transatlantic zest for scrapping and replacement is not universal, nor so great that appreciable exchanges can be detected during the period of active growth itself. Spiegelman, Monod and others find that proteins do not turn over to any important extent during the actual growth of ------ int, :- less important in the existence of non-dividing cells. is .d Hith of Bacillus subtilis. Bacterial spores achieve a relatively very stable non-dividing economy of low activity, but commonly the processes of ocui, The process of ageing and death in a unicellular organism is one of grcat interest and the subject of much controversy. A large population of unicellular organisms declines with timc according to a law t'rl from n=n.el, where cr at time i and a according to the state of the environment and the presence or absence of toric

·Ageing in Bacteria
7
of the previous history of the cell. The condition for the approxi.
mate applicability of the exponential decay law is then fulfilled.
This point of view, which stresses the dynamic nature of the
10.-
19
DISCUSSION
M. R. Droop. Does Professor Hinshelwood consider that there is any
profit in the analogy between ageing in the metazoan organism and the
bacterial culture as opposed to the bacterial cell?
...V. Ju JQUY LUNUrts the bacteria
are more nearly independent units but by no means completely so, and
their mutual interactions are significant in several ways.
O.V.S Keath By appropriate modification nf the onlin.
which y
large bu
This sug
multicel

·6 Hinshelwood In these conditions there could be an actual waxing and waning in the amounts of various enzymes or in the intensity of various functions of the cell. Something, analogous is mutatis mutandis 11. L:-1. or runs out. In the declining economy the chaos can be even worse. Some parts of the cell may even acquire phage-like properties and prey upon neighbouring parts. In such circumstances the waxing and waning of given pairs of enzymes, or types of cell material, might be likened to the changes of various animal species some of which prey upon others. In competitive systems of this kind, as Volterra showed, periodic changes in the numbers of the various species may be set up. When one species has plenty to prey on, it multiplies, and then consumes the prey so fast that this becomes scarce. Then there is a shortage of food for the predatory species which in turn dec w has a fresh opportunity to increase. the prey truly periodic with the cycles repeating themselves exactly, since this state of affairs would demand the fulfilment of rather precisely defined conditions, but a rough periodicity is quite plausibic. The periodicities will be multiple, applying to various pairs of cell units which can enter into relations analogous to those of predator and prey. These various periodicities, moreover, will be largely independent of onc another with their phases randomly related. In the declining cell economy there is no mechanism of adjustment, as there is in the gradual establishment of logarithmic growth, for harmonizing the amounts of the constituents with the various relevant rate conend. state. associated cnzyme activities and with independent frequencies, there will exist a certain probability that different functions (amounts or activities) will pass within a given short interval of time through a minimum value together. This probability is indcpendent of the previous history of the cell, just as the chanoc in a radioactive atom of that conjunction of events leading to disintegration is independent of time. Suppose now that when a given number of cell functions simultaneously drop to a minimum, viability is irretricyably impaired, that restitution becomes impossible and that death ensucs. Then the chance of death in a given interval of time is more or less independent ·AGEING IN HIGHER PLANTS Ву 0. V. S. HEATII Research Inshtute of Plant Physiology, Imperial College London, S.W.7 The mode of growth of higher plants differs so fundamentally from that of animals that the problems of ageing may be expected to differ in like degree. A perennial plant, such as a dicotyledonous or conferous tree, has all the working parts continually renewed, in LC-XATARA harma meristem (or embryonic zone) and from subsequent extension of the new cells so formed; the growth in girth arises mainly from new cells formed by a continuous meristematic layer, the cambium, which develops a short distance behind the terminal meristem and completely surrounds the shoot or root as the case may be. This nok: . - A Lubuvut pluvules a succession of pnmordia which yalan intense ULIN, 134), Uul Inese do not seem to play any active part in the life of the tree.) Thus the

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·Ageing in Higher Plants 11 Sequential changes in the kinds of leaf produced by the meristems It is well known that the early leaves of many plants show" youth forms ", often of simpler shape or with better developed laminae than those forraed later. This may apply to plants grown from cuttings as well as to those grown from seed. Thus cuttings of the hare-bell (Campanula rotundifolia) revert to the rounded leaf For the first few new leaves the later ones being linear. Early --- 2 rowers (see below). la many cases a breve. form" can, however, be produced by manipulation of external factors. Thus the hare-bell can be made to produce rounded leaves by low light intensity and the shrubby veronicas of New Zealand will produce leaf blades, which they lack in the mature form, in response to high humidity. The retention of the broad " youth form" of leaf by eucalypts grown in this country may be due to the same factors of low light intensity and high humidity. The fact remains that external factors cannot, apparently, prevent the "...th farme in arely formed leaves and thus a IA ADA modified by mantrial deficiencies (Gregory and Richards, 1929); in the fully manured plants each rate for the last-formed (10th) leaf ·10 Heath growth in some respects resembles reproduction, for the tree will have become an entirely new individual in the sense that a plant from a cutting or a tissue culture transplant is a new individual. The tree is in fact not unlike a coral colony though a much more highly organized "symbiotic community" (J. E. Baker) and apart from accident, discase and some mechanical and nutritional con siderations there seems no reason why it should not live indefinitely. The giant redwood trees of California (Sequoia giganica) show that this is not far from the truth, for specimens are estimated to have lived for some 3,000 years, attaining a height of over 300 feet and a diameter at breast height of 24 feet. Specimens of swamp cypress (Taxodium mexicanum) are estimated to be 4,000 ycars old. It would seem that the meristems should be ageless as they are renewed continually. Nevertheless they are found to show systematic changes with time and although some of these are undoubtedly caused by external factors others seem to be due to internal factors "" of the cambium, which od ", thus forming the e intimately connected 1951). Some tropical timbers grown in non-seasonal climates show no annual rings, but even so there is normally a pause in cambial activity with the shedding of Icaves and a renewal of activity with the expansion of new leaves (Simon, 1914, Coster, 1927-8 both cited by Richards, P.W., 1952T terminal m controlled appear to selves seem to be subject to inherent changes with time, not only in the periodical production in perennials of new leaves and of flowers but also, especially perhaps in annuals and biennials, in the kinds of leaves produced. In the latter types of plant the change over from purely vegetative growth to reproduction is associated with profound changes in the terminal meristems and is followed, after fruiting, by death; even in perennials there is normally, with the first onset of flowering, a marked check to vegetative growth and to the activity of those terminal meristems which remain vegetativc. The main problems of ageing in higher plants are thus, in order of increasing importance: (a) The ageing and shedding of individual organs. This is intimately bound up with (6) Inherent changes in rate of leaf production. (c) Inherent changes in kinds of leaf produced. (d) The change from purely vegetative growth to reproduction. Discussion of the first two of these problems is omitted owing to lack of space.

·Ageing in Higher Plants 13 terms of total dry weight the " efficiency index" since it measures the efficiency with which the plant uses its “ capital" as repre- • Height observed Loge heght oserved - Calculated flowers FLO wy) of any ebony quezd vad w w 3461 ZO 0 03:77 H: 5.412 e & 15 22 29 36 43 $0 $764 78 92 108 Days from germination FIG.1.-Approximately exponential growth in height of rain axis of cotton at Barberton, South Africa, season 1933-4. (From Annals of Botany. NS, 1, 1937, P 517.) growth of the hypocotyl making use reserves from the cotyledons- It may be noted that the relative growth rate in terms of height (a lineas measure) 13 one-third of that inte. The change give a clue net assimila on a basisc upward of ·12 Heath ܚܐ ܝ simple age series. The variation from leaf to leaf may often be much greater than the change with age in any one leaf. The apparent age drift " obtained from such a series of successive leaves is compounded of the effects of the positions of the leaves on the plant and of their ages; it bears no simple relation to the truc time drifts for individual leaves nor to the mean time drift for all the leaves. This warning is still frequently ignored. The change from purely vegetative growth to reproduction Some aspects of this change will be considered in rather more detail and since it greatly affects growth rates a preliminary consideration of growth relations may be useful. In higher plants the rate of growth in dry weight at an instant will be the net gain represented by the difference of the rate of assimilation (x) and the rate of respiration (Y); it will be completely determined by: 1. The assimilation rate (per unit leaf arca) = Y 2. The respiration rate (per g. of total dry weight) = y= 3. The ratio of leaf surface to total dry weight = 6 4. The total dry weight itself (B) which together with 3 specifics the leaf area A. If the first three were to remain constant over a period, then the assimilation rate would also be constant if expressed per unit of total dry weight (in view of the constancy of 3); hence the net gain per unit of total dry weight would be constant, i.c., the rate of increase in dry weight would be proportional to 4, the dry weight already achieved. The relative growth rate would thus be constant and growth would follow an exponential curve (Blackman, 1919). Since plant growth is largely a process of cell multiplication, this is the curve to which it will tend it all the cells, or a constant proportion of them, continue to divide and if they do so at a constant rate, i.e., if growth continues unrestricted by internal or cxternal factors. It seems most improbable that either of these two provisos would be fulflled for any long period. Further, in vicw of the differences in assimilation rates and respiration rates of successive leaves already noted, and of the mechanical necessity for a grcater proportion of supporting tissue as the total leaf surfacc cnlarges, it seems equally improbable that the values of 1, 2 and 3 above would remain constant. Nevertheless it is found in many cases that the relative growth rate is nearly constant, falling very slightly until flowering ensues when a sharp drop occurs. This was noted hy Blackman in the paper cited and he called the relative growth rate in

·Ageing in Higher Plants
15
crease in efficiency index.
TABLE 2.-(from Heath 1937b)
Mean quadratic regression coefficients (14-day) for logarithms of
total dry weight and of leaf dry weight
Season Total werghi Leaf weight
P*
1933-4 - 0587
00751
0001
1934-5 - 0464 -00545
0.1-02
*P=probability of the difference between the two measures being
due to chance.
Uh.....
to
nu
(C
Crowther postulates a " self-regulating mechanism " essentially as
wyludny Wiu De Considered here.
follows:
In the early stages of growth there are few positions where houde
ann fan
pivuutcu.
mbil le number of flower buds it
Boll (fruit) development followed with the resultant
Sexcre drain on nitrogen and also carbohydrates Growth then
ceased, and many of the florer buds and bolis were shed, Crowther

·14 Heath exhibit a small but significant downward trend, as shown by the quadratic regression of log {total dry weight) on time (Table 2). Since net assimilation rate showed no downward trend, this fall in . Flowers 4 Weight observed Loge meight observed - Calculated O . 30 -20 qw6} aybiam hup 8 607 (zvezd sad wh] aybian fuo 10 0-1005 T W.0 0429 15 22 29 36 43 50 57 64 28 92 106 Days from germination Fio. 2.-Approximately exponential growth in total dry weight of cotton at Barberton, South Africa, season 1933. (From Annals of Dolany, N.S. 1, 1937, p. 517.) efficiency index had to be attributed to a marked decrease which occurred in the ratio of leaf to whole plant (Table 1; data for to seasons are included). TABLE 1.- (from Heath 19376) Leaves as percentage of total dry weight of shoot Season Initial sample Al flowering 1933-4 77.0 54.7 1934-5 74.9 56-4 ·Ageing in Higher Plants 17 ound that simultaneously with the rapid transference of nitrogen 1 L L 11. 1 of the cotton plant show clearly that much or most of the putrogen For the bolls is withdrawn from the leaves. Nevertheless, the check o growth which occurs with the onset of flowering does not appear Co be solely a nutritional effect. In Fig. 3 are presented hitherto unpublished data for the mean (absolute) growth rates in height of 5 normal cotton plants and also for 45 simlar plants on the same plot from which all dower buds and developing monopodial lateral 5 446 ways of rais penod had no noticeable effect on the growth rate of the els ceaseu growth (24.3.31) it followed a trend almost identical with that of mean air temperature The curves shown for growth of the dishudded plants and mean air temperatures are fourth degree polynomials The total correlation hetwean th------ and correspond a value of r of seems clear th:

·16
Heath
2
Sulppnasio →
Flowers
Growth rate cmday
18
71
61
14
Feb.
24
Jan.
Mar.
April.
2
Growth rate om/day
706
Mean air temp. °F.
50
April
May
June
Fro 3.-Absolute growth rates in height of main aris of "normal" and "dis.
budded a cotton plants; also mean air temperatures, Barberton, South
Africa, season 1930-31.

·17
Ageing in Higher Plants
L.L. van
en-L.-.-.--.-
pour solu wunu all lower HUS alu developing monopodial lateral
shoots were removed every alternate day, when all the plants were
measured in the disbudded plants, then, the nutritional strain
ways, ou tous period nad no noticeable effect on the growth rate of the
disbudded plants Following first flower opening the growth rate
of the normal plants fell almost linearly to zero in 40 days; the
growth rate of the disbudded plants fell from the same date, scarcely
less rapidly for the first three weeks, and from the time when the
normalan 2
at the time for first flower
xung, even in the absence of an an
inherent change in the u
nature. Data for disbud

·<4 18 Heath more than four weeks before first flower opening in the experiment just considered. However, since barley is a monocotyledon with a terminal inflorescence and cotton a dicotyledon with a system of sympodial lateral flowering shoots some other differences in organi. zation may also be expected. Finally, the "minimum leaf number ", found before the occurence of inflorescence initiation in certain plants with terminal inflorescences, may be briefly discussed. Klebs (1918) postulated that until a plant had reached a certain stage of development and was ripe to flower "no combination of environmental conditions could make it flower; after this stage it would flower in response to appropriate external-conditions only. Clearly, if such a stage is rigidly defined it may at any time be disproved by the experimental exploration of new combinations of conditions, like any other null hypothesis. Thus Purvis (1934) and Purvis and Gregory (1937) found that in rye the number of leaves preceding the terminal inflorescence could be increased by environmental conditions up to about 25, but could not be reduced below seven. This was therefore accepted as morphologically defining the stage of " ripeness to flower". Much later Gott, Gregory and Purvis (1955) found that this number could be reduced to five by the use of continuous illumination. As the rye embryo already has four leaf primordia in the ripe grain and another develops during sprouting. This raised the possibilny that the plant was ripe to flower" immediately after germination and as soon as the first leaf emerging was exposed to light By prematurely harvesting grain, dwarf embryos were obtained with as few as two or three leaf primordia but the minimal number of leaves formed before flowering was still five. This was taken as evidence for an obligate vegetative stage, represented by the development of five leaves, which must precede flowering. In the onion the minimum number of leaves and scalcs so far found before flowering is about 13 (Heath and Holdsworth, 1948) and this leaf number may perhaps represent an obligate minimum for "ripeness to flower There is, however, a marked cllect of - bachne in plants prevented 1950) or plants The evidence suggests that initiation follow's when the plant has attained a sufficient size, and the temperature is sufficiently low (a mcan of about 12°C.), irrespective of total number of leaves and scales produced or of whether the plant has formed a bulb It is most unusual for inflorescence initiation to occur in onion sets (small bulbs) formed from plants which had fewer than five emerged leaves and this may well be a matter of integrated leaf area. Experimental cvidence was obtained for the production of an inflorescence-promoting hormonc, produced in the emerged leaves, stored in the swollen Jeaf bases formed when bulbing occurred and transferred slowly to ·Ageing in Higher Plants 19 the growing point during winter storage. Small sets when tipe normally have no swollen leaf bases but only swollen scales; larger sets and bulbs such as normally initiate inflorescences have one or man lan lanfhearam naman.-FA LLOJ...--- Cisewuere at the bulb Thus in the onion the effect of age on inflorescence initiation would seem to operate mainly through size attained (possibly leaf area) and if there is an obligate minimal leaf number it is generally exceeded There is no lack of interesting examples of apparent age effects on the change from vegetative growth to reproduction, for instance the simultaneous lorvering after many years of a plantation of Sisal (Agave sıslana) followed by death of the plants, but it seems more (ruitful to discuss experimental work when one is aware of its existence. References Allsopp. A 1953 ** Experimental and analytical studies of Pteridophytes XIX. Investigations on a farsilea 2 Induced reversion to juvenste stages Ann Bor, Lond, N.S. 17, 37-55, Ashby, E. and Wangermann, E. 1950. “Studies in the morphogenasis of leases IV Further observations on area, cell size and cell number of leaves ot Ipomoea in relation to their position on the shoot" New Phytol, 49, Djackman, V.H 1919 "The compound interest law and plant growth" Ann Bor Lon 33, 353-360 Coster, C 1927-28 "Zur Analomie uod Physiologie der Zuwachszonen und Jahresringhildung in den Tropen." Ann Jard bot Buirenz, 37, 49--160, 38, 1-114 Crowther, F. 1934 " igation is the Sud: anima Ure Gre **** Ally Didctem Gregory, ! G 1949 "The interaction of factors in determination of plant yrels" BnL Commonscalth Ses Official Conf. Plant and Animal Nutrition in Relation to Sorf and Climatic factors Melbourne.

·20 Heath Gregory, F. G. and Richards, F. J. 1929. "Physiological studies in plant nutrition I. The effect of manurial deficiency on the respiration and assint Jation rate in barley." Ann. Boi. Lond., 43, 119-161. Gregory, F. G. and Sen, P. K. 1937. "Physiological studies in plant nutrition VI. The relation of respiration rate to the carbohydrate and nitrogen metabolism of the barlav lanf no dete deficiency." Ann. Bot Goodall, D. W. and Grego an inder of their nutritt Tech. Comm., 17. Gnit AR Man ...1, 0, -16V Harris, J M. 1954. "Heartwood formation in Pinus radiata (D. Don)." New Plộ to, 53, 57-524, Heath, O. V. S. 1937a. "The growth in height and weight of the cotton plant under ficld conditions " Ann Bor, Lond., N.S. 1, 5i5-520 Heath, O. V. S. 1937h ** The effect of age on net assimilation and relative arniith mter of inn Bol Lond, N.S. 1, 565-566, Heat 18 talen Hold 15 Klet * Flora, 111/112. 140-IN. Purvis, O. N. 1934. "An analysis of the influence of temperature during ger of certain winter cereals and its inn Bor. Lond., 48,919-955. Purv Studies in the sernalization of cerenles Rich Dul, Lun, 40, 44-50 Richards, F. J 1938 " Physiological studies in plant nutrition VII, The relation of respiration rate to the carbohydrate and nitrogen metabolism of the barley leaf as determined by phosphorous and potassium supply." Ann Bor, Lond. N.S. 2, 491-534. Richards, P W 1992 The tropical rain forest Cambridge University Press. Simon, S. v. 1914 "Studien aber die Periodizität der Lebensprozesse der in dauernd feuchten Tropengcbicten heimischen Blume." 16. Miss Bul., 54, 71-187. Warcing, P. F. 1951 * Growth to cambial activity in ring-poro Wareing, P. T 1953. “Growth dormant buds of ragus sylve DISCUSSION Elizabeth Ilangerinann. There is more convincing evidence about ·21 Ageing in Higher Plants LA__1 any loss in growth potential, under conscaill and lavourable conditions. (Some of my plants have now been growing for five months at the same rate, and look like continuing indefinitely.) It seems therefore that ageing changes at the meristem occur in some groups of plants but not in others, and each will have to be investigated separately. - CVCHI SUL as pollination, The question of the mechanism of translocation of carbohydrate seems to me to he parent Tm La LA. L. . DELL VAC U TIM HOLT O. Y S. Heath. Although the flower buds may have had a high percentage nitrogen content the total weight of buds was very ema!? an that _ 1 I agree that the contrast between the continued growth over many months of the disbudded plants and the ranid fail nf the --- zero in the case of.. in nutrition brou: think, however, of growth, which plants, can be a sudden systemat Possibly hormon ·22 Heath - P. C. DeKock. Results obtained at the Macaulay Institutc show that, in ageing leaves, the phosphorus/iron, potassium calcium and citric acıd/malıc acid ratios decrease, as do also the respiration rate and the sensitivity of respiration to inhibitors, ageing lcaics often showing a stimulation of respiration in their presence This has been found for successive leaves on a shoot, as well as for the same leaf sampled at various times (tobacco, larch). There is considerablc evidence to show that cssentially similar changes in mineral composition, organic acids, respiratory rate and sensitivity to inhibitors, take place in all animal cells. H. W B. Barlow May I present some of Mr. A. C. Mason's results relating to the effects of age and leaf position on the mineral composition ... for A1. Ar curves obtained during the period of shoot clongation and those obtaincu when growth had ceased The latter set of samples shows the clfect of *t.h achicved being Icast in the lowest temperature, (h) the curves for cxtcn. sion in pure water and indolcacctic acid at 10, 20 and 30'C. show that temperature and growth substance are to some extent interchangcable, the 20°C. water curve being very similar to that for 10°C in indolescetic acid. When growth is rapid, extension is a good index of "asc", but at lower temperatures extension is slowed down more than " ageing ", so that these sections never attain the final length of those at higher fcmpcra. tures. Sections fransſerred from low to high temperatures never catch up . Com water later: chup cll as ertension has been arrested.

·AGEING IN ANIMALS Ву ALEX COMFORT Nuffield Research Fellow, Department of Zoology, University College London, W.C 1 AGEING US the name given to the progressive decrease in vigour LL mimo swith honaccoma of toma landing death increases with age, so that these forms have characteristic marimum life-spans In animals not subject to ageing, the probability of death would not increase, and the life span, though finite, would be indeterminate. I. continuously and have no fixed maximum size Animals of sharplyfired cell number which have no regenerative powers (rotifers, nematodes) tend to have an equally sharply-limited life span, One determinant of ageing may thus be the possession of cells which cannot be renewed by division and which deteriorate in the course of metabolic life Mammalian age processes may well, however, involve the production of new celis differing in quality and in responses from those which they replace Wear in irreplaceable structures such as teeth and wings, processes of accumulation, processes of depletion 2e in the nan Ein-1 effects of r animals cffects satiet 11411 a umiy oi causes, The rate of progress of age changes is a function not primarily of the passing of time but of developmental or metabolic activity (the " rate of living in min prolon the an has sh 1. W 1!Alunty of rats is prolonged by undera feeding, the animals can be kept fully active, but juvenie, for their normal lifespan and thta re-started in growth, the time gained in ·24 Comfort marking time effectively doubling the length of life. The life of rats once sexually mature cannot be prolonged to anything like the same extent (McCay et. al., 1941). These findings suggest that actuarial metabolism just as growth dpole. If this is so, one of search is to determine the components of the is programme of mammalian development biak . 6 ditterent types of vertebrate, so that age processes could be correlated with other physiological events. Such figures have been nunilohta monathan ts, and one There has xistence for captive birds, whose longevity is known to be much greater in proportion than that of m mals similar in size and activity. In some cases there are large differences in rate of development and life-span between animals of closely related species which could profitably be investigated if better actuarial data were forthcoming. One consequence of this lack of information is that we have no experimental mammal, intermediate in size and longevity bcuccn man and the small rodents, whose rate of agcing is accurately known. There are no published actuarial tables for rabbits or dogs. and only incomplete information for guinea pigs (Rogers, 1949). In consequence, many descriptions of physiological differences between young " and "old" animals are in fact descriptions of differences between infants and youngish adults. Apart from a limited number of spccies whosc ages can be deterch as scales vertebrates ade kennelbooks and stud-books, notes kept by breeders, and thc files of zoological gardens. Such material varics greatly in quality, and in most cases there are substantial losses 10 the record from salc, culling, or deliberate killing in the course of experiment In spite of this, it has already been possibic to obtain from these sources partial life tables for several breeds of dogs, and for a number of mammals and birds in zoological gardens. It is a common character of many of these mammalian populations that the curve of declinc is almost arith-lıncar, and the distribution of age at death is thereforc rectangular, a constant number of individuals dying in unit timc (Comfort, 1956b and 1957). In dogs, figures for Pchingesc, mastiffs and wolfhounds indicate a more rapid senescence in the than in small heade the median and maximum ages of these per cent from those recorded IL ·Ageing in Animals 25 Wild populations of small birds and mammals, and of many insects, commonly behave as if they were ageless, because the 1:21 * tn ho effectively age-independent, Haldane (1953) studies that the increasing age. vertebrate and specific age in + lnll the Phu NI LII4L contribution to the next generation of progeny has been made. Where few animals survive into late life, postponement of the expression of adverse genes may be equal in selective value to their complete abolition, and factors such as cessation of growth may be selected if they improve survival at the most fertile period of life, in spite of adverse effects in later periods Weismann originally might have been expected to be of selective advantage. References Allen, JA 1952 J. marine brol Ass , 31, 515. Comfort, A. 19569 The biology of senescence London. Routledge and Kegan Paul, Comfort, A. 1956 Proc, zool Soc. London, 127, 27, Comfort A 1057 Penn went S.. erp Zool. 76, 325 geing Baltimore Williams McCay, c. xi., Maynard, LA, Sperling, G and Osgood, 11.S 1941 J. Nutrit, 21,45 Melawar, P.B 1952. An unsoled problem of biology. London: H. K. Lewis Rapson, AM1952 Austr. marine Freshw Res, 3, 170. Rogers, J. B. 1949 Anat Rec , 103, 498.

·24 Comfort marking time effectively doubling the length of life. The life of rats once sexually mature cannot be prolonged to anything like the same cxtent (McCay et. al., 1941). These findings suggest that actuarial senescence is dissociable from total body metabolism just as growth and metabolism are dissociablc in the tadpole. If this is so, one of the most important problems of age research is to determine the components of the programme * of mammalian development which act as timekeepers in initiating the senile decline. It might become easier :- for the greatest possible different types of vertebra' lated with other physiological events. Such figures have been available nmnnn yartahening 'nts, and onc or: There has bee oxistence for captive bırds, whose longevity is known to be much greater in pro- O. .. Lo mvestigateu 11 Delter actuanal data werc forthcoming. One consequence of this lack of information is that we have no experimental mammal, intermediate in size and longevity between man and the small rodents, whose sale of ageing is accurately known. There are no published actuarial tables for rabbits or dogs, and only incomplete information for guinea pigs (Rogers, 1949). ological differences fact descriptions of Apart from a limited number of species whosc ages can be determuned by inspection of annually-increasing structures such as scales or horns, it is evident that studies of ageing in long-lived vertebrates must be based chiefly on existing records. These include kennelbooks and stud-books, notes kept by breeders, and the files of zoological gardens. Such mate arics greatly in quality, and in most cases there are substantial losses to the record from salc, culling, or deliberate killing in the course of crperiment. In spite of this, it has already been possible to obtain from these sources partial life tables for seseral breeds of dogs, and for a number of mammals and birds in zoological gardens. It is a common character of many of these manimalian populations that the curve of decline is almost anth-linear, and the distribution of age at death is thereforc rectangular, a constant number of individuals dying in unit time (Comfort, 1956b and 1957) In dogs, figures for Pckingesc, mastills and wolfhounds indicate a more rapid scnescence in the large than in small breeds; the median and maximum ages of these pedigree breeds differ by less than 20 per cent from those recorded in dingocs and in Wolves.

·AGEING AND METABOLISM By FRANÇOIS BOURLIÉRE Laboratoire de Physiologie, Faculté de Médecine, Paris A LIVING organism being, as von Bertalanffy (1949) so aptly defined it, a graded structure of open systems which maintains itself in accordance with its inherent principles while its constituent elements are constantly changing, one may ask if the rate of renewal of these in poikilothermic invertebrates and vertebrates, which lack the efficient thermoregulating and other homoiostatic mechanisms which Keep the milicu inténeur of homoiothermic vertebrates so remarkably constant and almost insensible to the usual variations of their environment. In such lower animals, the conditions which are theoretically able to modify the energy-turnover are numerous. The first to be considered--and the first which has been studied experimentally—is the environmental temperature. But many other fomno Ph. Such a susceptibility to the variations of the environmental conditions is nevertheless not restricted to the "lower” animals. Tommarna. Soule Insectivora and lower Primates) and the ageing processes of such abnormal forms are well worth investigating from the stand- Imertebrates In spite of the scarcity of information on ageing processes in invertebrates a few well established facts seem to indicate that there 16 among them a definite and inverse relation between metabolic fales and speed of growth, and duration of life.

·26 Discussior: DISCUSSION W. B. Yapm. Could Dr. Comfort tell us a little more of his reasons for making tuo staterents which go rather beyond the evidence that he has presented to us? The first is that we have no life tables for birds, ubereas there are in fact sencral for wild populations, so that he seems to imply the assumption that a life-table is only of value when it applies to captive animals. The second is that while it is probable that birds potcou3Ily suffer from old age some cold blooded vertebrates may not; the life tables of wild birds provide no evidence for the first part of this vica, while the ancodotal evidence of long-lived repuls and fish mean nothins more than that the potential maximum age us high. A. Comfort. There are in fact life tables for birds in the sid, but it is not possible to study senescence in populations which do bot live long enough to reach senescence. There is no we table for birds under from tected conditions, and so far populavon Rork on birds such as the albatross, which probably reach seriescence in the wild, has not been in progress long enough to be of significant use to us. I think it will probably prove to be correct that the majority of poikilotherms ultimately undergo senescent change. Jf we were to find animals in which ibe polconal biespan were so long that it could never be exhausted by any significant number of animals in a population, enquiry about their potential senes. cence would be a little academic. Perhaps I may take indeterminacy of age to mean sumply the behaviour of animals in which no increase in vulnerability with age has been detected honeter long they have lived. JL. Cloudsley Thompson. Insects and other terrestrial arthropods Icry at constant temperatures tend not to live so long as control animals in fluctuating cnvironmental conditions The subject has recently been reviewed (Cloudsley-Thompson, J. L, 1934, Entomologui, 86, 183-9). monde so rapidly (Cloudsley-Thompson, J L., 1953, Anu Mog. Nar Hist. (1), 6, 705-12 RL Worrall. Since old people, generally speaking hait less protcin than when they were young, there must be an overall cucess of protein combustion picr protein intake, for the period of adult life as a whole This long-term net loss of body procin is too gradual and intermittent to hola rimtione Immon. mental error in nitrogen balance studios. It is possible, however, to estimate the tendency of human adults towards protein deficiency, by measuring the percentage of total basal Ihr poblished 19 of Yoitin in human adults an be minimized, so that a serious degikt vi tissue atrophy is postponed, and actise life is thus prolonged ·AGEING AND METABOLISM Ву FRANÇOIS BOURLIÉRE Laboratoire de Physiologie, Faculté de Médecine, Paris A LIVING Arne - accor are cc eleme S. mully other 14LK the UWC homoiostatic mechanisms which MU meu intérieur of homoiothermic vertebrates so remarkably constant and almost insensible to the usual variations of their cnvironment In such lower animals tha theorctically ahlata first to t mentally factors a wwwulil. Seasonal changes of activity and food consumption, hibernation, aestivation and reproductive activities are all able to influence the rates of vital processes. Such a susceptibility to the variations of the environmental conditions is nevertheless not restricted to the “lower” animals Temperature variations for instance may have an obvious influence on the metabolism of some burds (swifts, nightjars and hummingbirds) and mammals (most marsupials, edentates, bats and even some Insectivora and lower Primates) and the ageing processes of such abnormal forms are well worth investigating from the standpoint of comparative gerontology It is the purpose of this paper to review briefly the evidence at hand on the correlation which seems to exist in the animal kingdom between the rates of energy-turnover and ageing. Invertebrates In spite of the scarcity of information on ageing processes in invertebrates a few well established facts seem to indicate that there is among them a definite and inverse relation between metabolic rates and speed of growth, and duration of hfe.

·26 Discussion DISCUSSION IV. B. Yapp. Could Dr. Comfort tell us a little more of his reasons for maling two statements which go rather beyond the evidence that he has presented to us? The first is that we have no life tables for birds, whereas There are in fact several for wild populations, so that he seems to imply the assumption that a life-table is only of value when it applies to captive animals. The second is that while it is probable that birds potentially suffer from old age some cold blooded vertebrates may not; the life. 1.1. f...L. A. Comfort. There are in falfo alla fa-Li that h... it is not possible to study senescen enough to reach senescence. tected conditions, and so fa albatross, which probably reach senescence in the wild, has not been in progress long enough to be of significant use to us. I think it will probably number of animals in a population, enquiry about their potential senescence would be a little academic. Perhaps I may take indeterminacy of age to mean simply the behaviour of animals in which no increase in vulnerability with age has been detected however long they have lived. IL Cloudsley-Thompson Insects and other terrestrial arthropods kept ---t--animale in 6, 705-12. R. L. Worrall. Since old people, generally speaking, have less protein than when they were young, there must be an overall excess of protein combustion over protein intake, for the period of adult life as a whole. This long-term net loss of body protein is too gradual and intermittent to Irmann, . towards protein deficiency, by measuring the percentage of fuldDUSU Like in human adults can be minimized, so that a serious uogice v Ljuuu atrophy is postponed, and active life is thus prolonged.

·29 Ageing and Metabolism dividuals *41 TS animals was on the other hand distinctly abbreviated and the duration of life of the imago (which never takes food) remained unchanged. It thus appears that the prolongation afi'ra fot.: by intermittent starvationc Subsequent experiments by over show that food restric . UM DIVJpnu merunuguster never incrpnre the imnninntir... Why wou ALP! 111 a suitable (moist and not too hot) environment. Among rotifers the life span of the adults seems likewise to be inversely proportional to metabolic rate. Encysted adults may Sunive as long as 59 years in diapause (Rahm 10771.11. The feneth P.1. flic. tro butterure А - rupu uiry in their third ·28 Bourlière MacArthur and Baillic (1929a) used parthenogenetically produced males and females of one pure line of Daphnia magnia and kept them at various temperatures (8, 10, 18 and 28°C.) the other conditions remaining constant. In such experiments the mean length of life of these cladocerans was strongly influenced by temperature. The correspondence between mean Itſe-span and temperature is illustrated by the following figures: 25.58640 28 days at 28°C., 41-675+0-35 days at 18°C., 87.8£1.98 days at 10°C. and 108.18-2-43 days at 8°C. The temperature coefficient for longevity averaged 2:12, which closely approximates that for most chemical reactions, but the Q10 values were higher (2059) in the lower ranges and lower (1.64) in the higher ranges of temperature. It is to be noted also that the duration of life in males responded morc sensi. tively and more extremely to temperature alterations than did that of females. At the same time MacArthur and Baillie (1929b) found that clcvation of temperature from 8 10 18°C. increased the heart rate and the susceptibility to potassium cyanide by a little over two and a half times, and this acceleration of metabolic rates was associated with a very nearly proportionate decrease in duration of life. It was also noted that the duration of life of females exceeded that of males, corresponding to a sexual difference in metabolic rates. These results are confirmed by the findings of Terao and Tanaka (1930) on another cladoceran Monna macrocopa. The maximum duration of life of this species takes place at about 15°C. (14.36+ 0.38 days), and gradually decreases at higher temperatures (9-285 0:18 days at 21°C.; 6.51 +1.67 days at 27°C.; 4.77_006 days at 33°C.). It is interesting to note that below 15°C. the life-span does not increase any more. Alpatov and Pearl (1929) have investigated the effect of the temperature during development and imaginal life upon the duration of life of Drosophila melanogaster. Their results show that the effect tures and in both sexes, with but one exception. For instance females reared at 28°C. had a mean duration of life of 28.52-0:34 days, while the ones reared at 18°C. Iived 70-61+-0.98 days. The --- --- -. upon the duration of life "he environmental temperaa shorter time. This last xperiments hy Locb and Northrop (1917). Another cxperimental way to influence the metabolic rate of invertebrates is by food restriction. Such a method has been widely ·Ageing and Metabolism 31 . ---L'L'ns and rentiles being less data 1) has nevertheless given us recently sure I WILL.... on on Dorth American species. The duration of the larval period of some widely distributed toads varies greatly with latitude In North America the bullfrog (Rana catesbeiana) undergoes metamorphosis at the end of the first L autooma northern nart of its range but nole ..hataruni ittern cent 1 Were itural 114 117THC au they grow throughout their short life-span On the other manu, be determinate in one part of the animal's range and indeterminate in another. Similar data are lacking for snakes and turtles, most unfortu- Dately since these are the longest lived of all vertebrates. Seasonal variations of environmental temperature do not affect greatly the thermal constancy of the milicu intérieur in most warmblooded vertebrates. The temperature factor has less effect on .L sprvinw methaliemte olmnat no one line.

·30 Bourlière Rance river where food is abundant, the growth is very rapid and the limpets reach a very big size, but die when two-and-a-half years old. On the other hand those living on exposed rocks along the coast, when water is less rich in organic material, have a very slow growth, reach a smaller size but live much longer (up to sixteen years). Vertebrates The prolonged life span of most vertebrates does not favour an experimental approach to the supposed correlation between the rates of energy-turnover and ageing We must rely on available information patiently gathered by ecologists and field-naturalists. It is not usually possible with such data to attain standards of precision comparable to well controlled laboratory studies. But they nevertheless give us some insight on the way the environment can differently influence the life-span of various populations of the same species. position can be made in most cases On the other hand some species have a rather wide geographical distribution and live in waters whose temperature and food-content varies greatly. In such conditions striking differences in growth rate, tempo of life and (194 Am ----.1.. - Atv ife. ifc. On the contrary the arctic subspecies found in Great Bear Lake (Thymallus signifer signifer) does not reach its scxual maturity before Hann mun ... reach their maturity pilchardus) have a st live longer in the En Vigo. ) Jannatus (rujic lower (1935) de Luz and ·Ageing and Metabolisme 31 Age determination in wild amphibians and reptiles being less reliable than in fishes, and in most cases quite impossible, the data on these two classes of vertebrates are scanty. Oliver (1955) has nerertheless given us recently some very interesting information on north American species. The duration of the larval period of some widely distributed ... 1 lilc.cycle in the two cases is altogether different. Among lizards striking latitudinal differences in growth-pattern CHUMICU IU WU veurs I his warm climata - ..., WAJ U. tiir Whan one al forc necessary to infer with respect to determi be determinate in one I in another. Similar data are lacking for snakes and turtles, most unfortunately since these are the longest lived of all vertebrates. Seasonal yashauons of envirotimental temperature do not affect greally the thermal constancy of the milieu intéricur in most warmblooded sertebrates The icmperature factor has less effect on the energy metabolism of these animals than for inetnan .. resinetinn dem--, ·32 Bourlière but continues throughout life; it is significant to find that these mammals whiclı have a northerm Ociober 1938 jurlière 1947). sole recenty Dorst (1954) reported cases of marked Rhinolophuis ferrum.onuim.... nad 1:.... : reached respectik longevities of 8 to Is appears that in these mammals a reduced energy-metabolism and a low ſecundity is definitely associated with a long life-span. Inversely, shrews, with their very high metabolic rate and fecundity are among the shortest lived mammals. A very similar state of affairs seems to exist in some birds like swifts, hummingbirds and nightjars. Such are the facts which suggest at the present some kind of correlation between rates of energy-turnover and ageing. Since the work of Rubner (1909) and Pearl (1928) our knowledge has slowly progressed and the influence on ageing processes of such factors as the rate of living", the "temno of life and even ile well find their comn on metabolic rate. than a certain fixed and the rate of this energy-turnover appears to determine the rate of ageing. If such a correlation is confirmed by more extensive experiments and observations it will remain to understand its underlying biochemical and biophysical causes. Some recent experiments showing that enzyme molecules liave a definite life-span already suggest new approaches to that highly complex problem. References Alpatov, V. Want Bertalantly, L. Bishopp, FC 78. Bourlière, F 44 US116, II, III. Brown, C JD. 1943 Wildlife Algmi , 7, 353 Comfort. A. 1956 The brology of senescence. London, Routledge. Dorst, J. 1954. Mramnialia, 18. 231. Fischer-Piette, E. 1939. J. Conch., 83, 303. Flower, S. S 1935. Proc. 2001. Soc. London, 265. Fountaine, M. E. 1938. Entomologist, 71, 90. Ingle, L. 1933. Science, 78, 511. Innla 1 Wand Tradni 1937. J exper. Zool, 76, 235. ple, 46, 1. 4 ·33 Ageing and Metabolism 1.1,- 1 El Chem, 32, 103, 9a y exper Zool., 53, 221. 96. J. exper. Zool, 53, 243. North American Amphibians and Janes TILILCIUIL, JU NUSIA JUU Panimo ops er und sesse Beziehung zu ,0, 25, 67. DISCUSSION J B. Hamilton The studies of Dr. Clive McCay, as mentioned by Dr. Comfort, suggest that an irreversible form of ageing Occurs upon maturation of rats, whether the animals have been starved previously or not. Somewhat similar findings have been reported in some invertebrates (Kopec, 1924) but not in all (Bishopp and South, 1938). This point deserves further study ponarially with refornserual nature protoplasmic re - RL Worrall. An animal's energy turna buildin 1 ·34 Discussion demonstrated for a wide variety of tissues, ranging from the brains of bees to the muscles of men. The length of adult life, in man and other mammals, is thus a function of three variables: 1. The energy turnover. 2. The net loss of protein per unit of energy turnover. 3. The minimum amount of protein required for life. With approximate numerical values for these variables in different animal species, the general factors determining the length of adult life can be handled mathematically, TYL : 1. The energy turnover. 2. The net gain of body protein per unit of energy turnover. 3. The maximum amount of body protein allowed by negative physiological feedback. Each of the above variables is itself a function of others, the definition of which is a major task of biology,

·THE AGEING OF MAMMALIAN CELLS
By
GEOFFREY H. BOURNE
Department of Histology, London Hospital Medical College,
London, E. I
The rates and the methods of ageing of mammalian cells appear to
be different in various organs and tissues. Because of this fact
Cowdry (1952) classified the cells of the body from the point of
Niew of ageing as follows:
V-- ---
1
... C.Iuclicc vi age change.
r.--..
w...) vt schaul as locy approach the surface.
3 Rantinopt-'.
.
VI,
We july, even in quite old animals they may rejuvenate in
the sense that they undergo a series of rapid mitoses, and the relatively
undifferenuated cells that result can differentiate into normally
functioning cells of that organ. The cells of the liver, kidney,
thyroid gland and salivary glands come into this category.
4. Tited met mitt -

·36 Bourne fresh gro protein) comes to an end because the synthetic capacity of the existing C ation of DNA however, las pointed out that a theory of upon the exhaustion of cell catalysts. Although cells of various tissues age in different ways and rates they are normally present in this condition, when the cells are taken from an old animal. Whcther this is the result of increased fragility in response to mechanical handling of the tissue or to the fixatives used or whether they are in this state in the living coil cannot be stated with certainty. Furthermore, in old cells it is always more difficult to demonstrate mitochondria because there appears to be a 11.1 :'walls of blood wls Payne has described changes in the mitochondria. At first they enlarge, then become vesicular. Many of them then ſuse to form a single large body and at this stage the cell usually dies, the “ chondrosphere being liberated into the intercellular spaces. In the cells of the germinativum in ageing skin there is a reduction in the number of mitochondria Tissue culture cells, provided they are constantly of cells is not unusual. If sub-culture is not carried out, however, degenerative changes followed by death occur. Charactcristic amongst these are mitochondrial changes. These normally filamentous organelles break up into rods and granules or swell into small vesicles and there appears to be a nett decrease of mitochondrial substance. It may be significant that similar changes occur in "MISLI). , at least salivary Andrew (1951). These mitochondrial changes are of considerable significance. It is known that something like 80 per cent of the enzymes of the Krebs ·The Ageing of Mammalian Cells 37 cycle, which are responsible for the aerobic metabolism of the cell and which supply the energy required for oxidative phosphorylation, are found in these organelles ; substantial alterations in their form and quanlity must have a fundamental effect on the metabolic activities or the cell. Fragmentation of the Golgi apparatus is also characteristic of degenerative tissue culture and aged tissue cells. For example, Suſkin and Kuntz (1952) have shown that in the ganglionic nerve cells of young dogs the Golgi material is composed of a loosely michal with the same staining reactions as the Golgi substance, but where it occurs it is in the form of discrete granules. It is likely that electron microscope studies will tell us a great deal more about the structural changes in both Golgi material and mitochondria in old age. In degenerating tissue culture cells characteristic nuclear changes occur. The nucleus may divide without mitosis into two or more parts (Andreu (1955) claims to have seen evidence of amitotic division in Ihe nuclei of the cells of the brain in old animals). Vesicles of nuclear sap may be squeezed out into the cytoplasm. In some cells the nuclear wall may break down and the whole nucleus may liquefy. In old nerve cells the nuclei may become pyenotic and show a decrease in nuclear histone which, according to some authors, suggests a diminished capacity on the part of the nucleus to synthesize nuciec acids In addition to pycnouc changes the nucleus may show an internal brushuork arrangement attached to one side of the nuclear membrane, and the nucleoli may show a honey-combed rim. Tycnotic nuclcs have been described in many of the organs of old animals by a number of workers. Meyers and Chanpper (1956) desenbe nuclear scsicles in the cortical cells of the adrenals of ageing hamsters. In the cells of the autonomic ganglia of old dogs there seems to be a loss of chromidial substance iniben and '. the form of a pripheral chr and displaced and the cells there is a shift in the nucleo nucleus. It is of nterest th mort resistant to age chan Hun ledures characteristic of ageing ayfonomic ganglia. Cell membranes appear to alter with old age; certainly their permeability alters and presumably this indicates some structural modification Nos sery much work has been carried out on the permeability of mammalian cells-Lansing's wosk (1947) on per meability of old cells was carried out with Spirogyra. It is of its har he found ot ·38 Bourne same direction for all compounds, for example, old cells were more permeable to alcohol and less to urea. This may also be true of the cells of the gastric mucosa of old human beings, at least for alcohol. As long ago as 1917 Herzfeld and Klinger showed that there was an increase of protein at the surfaces of old cells and that this interfered with the normal free exchange across the membrane. of old human tissues, e.g. brain, sclera, arteries and elastic tissue is an increase of 'his excess of iron reached a maximum in the rat at about 11 years of age and thereafter it remained constant for the rest of the life of the animal (3-4 years) This increased iron content was found only in the cells of cpithelial organs, not, for example, in muscle cells. The authors discussed whether this increase of iron was of special significance or whether it was dependent on the destruction of blood during the lifetime of the animal. They claimed that this increased iron was not due to haemosiderosis, pointing out that it occurred uniformly in organs in which haemosiderosis does not usually occur. The low values for iron in young animals and the high values for old animals were found to be constant If the deposition of iron was due to destruction of blood one would expect the deposition of iron to be continuous throughout life--whereas this is not so. The authors quote this evidence therefore as proof that the increase of cell iron up to 14 years of age must have some functional significancc. They point out the remarkable constancy of their results; that the increase of cell iron at various ages is so regular that it is possible to tell the age of an animal by an iron estimation They believe that the extra iron accumulated by the cell probably forms a compound other than those already present in the cell. It is of interest that changes occur in the haemoglobin iron of old mammalian erythrocytes (Lemberg & Legge 1949). In fact the ageing of erythrocytes is said to be due fundamentally to exhaustion of the system which maintains haemoglobin iron in the ferrous condition. It might be thought that this was due to the absence of a nucleus from the crythrocyte, but the avian crythrocyte, which possesses a nucleus and which appears to be able to synthesize haemoglobin continuously while the cell is in circulation, has a shorter life than the mammalian erythrocyte.

·39 The Ageing of Nannalian Cells LL. .fol. m11. afr. cell. It is of interest that in vitamin E deficiency pigment occurs in many cells and some authors have thought that the so-called senility \r Ja cilil in paraltin sections. It was subsequently shown that This pigment was acid-fast (Endicott and Lillie, 1944). It also fluoresccs a greenish yellow with the longer wave-lengths of the ultra-violch. Only pigment which has these properties is entitled therefore to be called " ceroid". Pigments of this type have been found in ar sraumland. One would expect that as cells age there would be a decrease in the various enzyme systems present in them. The falling off of oxygen consumption itcorded by various authors (sce Shock and Yicngst, 1955) surgests that thie minhther I lungs. Despite these findings, howeser, my own preliminary histochemical preparations of young and old animal tissues indicate a slightly increased sucrinic dehydsuggesting to activities oil A further faction of ! ! !

·40 Bourne seventeen different organs in young and old rats. Preliminary observations indicate not a decrease in these hydrolytic enzymes in the tissues of old animals but rather an increase. This is most marked in the cerebrum and cerebellum (particularly in the Purkinje cells), in the brush border of the duodenum, and in the seminal vesicles; it was present but less marked in organs such as the liver and kidney. The substrates used for the phosphatases included slycerophosphate, which presumably demonstrates what is colloquially called "alkaline phosphatase" (which is, in fact, a non-specific phosphomonoesterase), oestrone and cortisone phosphates, pyridoxal phosphate, carbamy! phosphate and ethanolamine phosphate. The enzymes which dephosphorylate these latter compounds although having their optimum pH in the region of 8 or 9 appear to be quite distinct from the non-specific“ alkaline phosphatase ". The histochemical preparations which are obtained from their use are quite different from those obtained with the latter, So far as is known at present, oestrone and cortisone phosphates are not formed in the metabolic processes involved in the in vrro metabolism of these compounds, so that the increased dephosphorylation of them in older tissue may simply be an aspect of incrcase in general phosphorylytic activity in these tissues. On the other hand, of the remaining three, two (pyridoxal phosphate and carbamy! phosphate) are metabolically important substances, while the rôle of ', distributed sciated with e prosthetic group of several, and possibly all, amino acid decarboxylases, carbamyl phosphate is an important intermediary in urca synthesis in the body--it acts as a carbamyl donor in a variety of enzymatic systems. 1.1 physiologically very important substances towards the latter. It may be argued, probably quite justifiably, that histochemical preparations are artefacts and what goes on in them bears little relation to .--.horoculte ohtniner by ich IVC he rk, ICS ch appear to be microsomes and in which most of the hydrolytic enzymes appear to be concentrated. Among these enzymes were B-glucuronidase, acid phosphatase, cathepsin, ribonuclcasc and deoxyribonuclease, and the name given to these bodies was "lyso·somes" The Ageing of Mammaliars Cells 41 In a lecture at University College during 1956 de Duve described these bodies colloquially as "sucide bags and claimed that their unrestricted activity after death was the cause of tissue autolysis The increase in activity in these bodies in old tissues either by loss of inhibitory control or otherwise may help to erplain the progressive inefficiency and degeneration of tissues as they age. Cytolytic activity resulting from the activity of lysosomes may be responsible for the loss of neurones from the brain in older animals. Purkinje cells in senile tissues for every 41 in the young animal. -rmor-1. tollowing numbers of Purkinje cells per given area of cerebellum in men of different ages: 42 years, 823; 65 years, 691; 79 years, 500; 94 years, 462; 100 years, 465. Sulkin and Weatherford (1955) have shown that in autonomic gangiia in old dogs there is a decrease in vitamin C (as demonstrated by the acetic silver nitrate technique), changes in the Golgi apparatus, and accumulation of pigment and substances positive to the periodic Schur reaction They also showed that similar histochemical changes could he needed in ..." a vitamin C vitamin C old age res We wil. Suyu ve We enciency of the enzyme systems synthesizing this vitamin. It also raises the question as to Whether partial deficiency of this vitamin over a very long period of time ia human beings might not play a part in the initiation or acceleration of tissue changes usually attributed to the process of ageing. Although it has been suggested that increase in hydent. --- activity in old age m. of the tissue degener problem of the contre number of organs d and it is also know cozyme activity and (1953) showed redt kidney, liver and castration, and Brandes and Bourne (1955) showed loss of acid ***as Ilowing adrenalectomy and phosphatase from the Golgi region of the mouse prostate following castration, and its return to that site following implantation of testosteronc.

·40 Bourne seventeen different organs in young and old rats. Preliminary observations indicate not a decrease in these hydrolytic enzymes in the tissues of old animals but rather an increase. This is most marked in the cerebrum and cerebellum (particularly in the Purkinje cells), in the brush border of the duodenum, and in the seminal vesicles; it was present but less marked in organs such as the liver The substrates used for the phosphatases included and Vintney Puur enzymes which dephosphorylate these latter compouilus imub ... of parenrincar to be quite ". The histor use are quite So far as is known at present, vesil one anu wargne phosphates are not formed in the metabolic processes involved in the in vivo metabolism of these compounds, so that the increased dephosphorylation of them in older tissue may simply be an aspect of increase in general phosphorylytic activity in these tissues. On the other hand, na ihope, two' (ovridoxal phosphate and carbamy! phospliolipid melayuisis. yorum sonna nf <pveral and possibly all, amino acid decarboxylases, cara pernih cis in the ystems. ated in old tissues may be of considerable suguvun S. ndicate mhift in the balance between synthesis and hydrolysis of these kin lottar It may n ren the biochemists work they specialize, namely tissue homogenates, we unu in g... recorded an increase in other types of hydrolytic enzymes in the tissues of older animals, namely B-glucuronidasć (Byrbye and Kirk, 1956) and acıd phosphatase (Zorzoli, 1955). In this connection it is of interest that de Duve and his colleagues (1955) have described in cells of rat liver a series of bodies whicłı appear to be microsomes and in which most of the hydrolytic enzymes appear to be concentrated. Among these enzymes were B-glucuronidase, acid phosphatase, cathepsin, ribonuclcase and deoxyribonuclease, and the name given to these bodies was "lyso-

·43
The Ageing of Mammalian Cells
"It is possible that some of the age changes in nerve cells might be
reversed with hormonal or other stimulation but no hormones will
be able to bring back to the brain the cells which have already been
lost by the ageing process,
If many of the ageing changes of tissue cells are due to failure of
...vu upuupuy or te uver, heart and
spleen, that is the hypotrophic process of old age has been reversed.
When thyroid hormone was used in addition to the anterior pituitary
hormones there was a beneficial effect on all the organs studied
Terlerine oland
References
Andrew, W. 1955. J. Grront. 10.
Byteman, F. and Papez, W. 1951, Geront , 6
Blumenthal, HI T. 1955. Geroni.. 10,235.
Boume, G. ll. and Malaty, HA 1953. J. Physiol. 122, 178
Brandes, D and Bourac, G. H. 1954 Brt. J. exp Path, 35, 577,

·42 Bourne Many papers in the literature have demonstrated the relations between morphological and biochemical changes in tissue cells and steroid and other hormones. In senescent humans and animals it general increase of connective tissue in pituitary, adrenals and thyroid, in the pituitary she found an increase of basophil and chromophobe cells, in the thyroid loss of colloid or poor quality colloid and reduction in the size of cells. In the adrenal accumulation of what appears to be ceroid pigment and degenerative changes in the cells were found. A number of authors have studied the changes in these three endocrines in a variety of animals (scc Blumenthal 1955) and degenerative changes in the reproductive glands are also well known and frequently recorded. It may be, therefore, that tissue changes in age are due to progressive degeneration of the endocrine glands. Korenchevsky and his co-workers have shown that multi-hormone preparations can retard or reverse some but not all of the weight changes in organs due to age, and in some cases they aggravate the senescence changes, Other workers have also studied the response of old tissue cells to hormones Shock (1956) for example says that in tissues in old individuals which remain functional the response to steroid hormones judged by the N, K, P and Ca balances is the same as in the young subjects. Another investigation in this field was that of Masters (1953) who records the effects of sex hormonc treatment of female patients who were over 60 years of age and who were all at least ten years past the menopause. These patients were followed until eleven of ihem died and autopsy material was obtained from the reproductive organs. The uterus and cervix were found to be increased in size and to be comparable in this respect with the normal for women between 20 and 40 years of age. The vagina was returned to a state identical in appearance with that scen in the fully functional vagina and reactivation of the cells of the breast was also obtained. Although microscopical section showed a reactivation of the blood vessels in the ovary the latter did not show a contween They pointed out that the capacity for growth in cpiphyseal cartilage declines with age and eventually ceases completely. On the other hand articular cartilage remains able to proliferate. Thus articular cartilage at any given age is in a younger statc physiologically speaking than the cpiphyscal cartilage. The latter has in fact Annet from this houver. ---Li.

·The Ageing of Manimalian Cells 45 because cell division finishes while the leaf is tiny and the development of successive leaves is mainly just cell expansion, During this expansion F Dichy W Annan Anul n.1.. ULLU wulu symptoms G. H. Bourne. I have no comment. R. J. Ludford Several references have been made during this conference to the significance of mitosis in the ageing of organisms. Dr. Comfort suppetect that one datarman.r. The results of tissue culture work sprest that rallo - u silvilies are limited to a ... u-uuplication. Aberrations of mítosts are frequent, and result in irregular distribution of chromemor neahhi ·44 Bourne Rurhus and V:.1. I at Various Ages. Oxford Medical Publications. Cowdry, E. V. 1952. In Cowdry's Problems of Ageing, revised by Lansing. Williams & Wilkins. De Duve, C. et al, 1955 Biochem. J., 60, 604. Ellis, R. S. 1920. J. comp_Neurol., 32, 1. Endicott, K. M and Lillie, R. D. 19:44. Amer. J. Path , 20, 149. Gatenby, J. B. and Moussa, T. A. 1951, J Physiol., 114, 253. Harris, A. 1927. Zool. Anz., 74, 249. Hartroft, W. S 1953 J. Geront., 8, 158. Hertzfeld, E. and Klinger, M. 1917. Biochem 2, 83, 42. Hodge, C.F. 1894. J. Physiol. 17, 129. Korenchevsky, V. and Paris, S. K. 1952. J Path Bact., 63, 111. Kurtz, S. M and Andrew, W. 1951 J. Geront, 6. Lansing, AI 1942. J. exp. Zool., 91, 195, Lansing. A. I. 1947. J. Geront., 2, 228. Lansing, A. I. et al. 1949 Arch Biochem, 20, 125. Lansing. A. I, 1952. In Coudry's Problems of Ageing, revised by Lansing Baltimore, Williams & Wilkins Lembers, R. and Legge, J. W. 1949 Hemalın compounds and blle pigments. New Vol. I-ama-- D.Liene an. Lindop, P. London. 1:11. 'n 1956 Anal. Rec , 124, 1. Pelc, S. R. and Howard, A. 1953 Exp Cell Res Surpl., 11 Shock, N W 1956. In Hormones and the Ageing Process New York, Acad. Press. Shock, N W and Ylengst, MJ 1955, Geront., 10, 31. ILA J. Geron!, 7, 399. Science, 86, 269. TS Geroni., 7, 533 (Unpublished ) chem J, 28, 587. . DISCUSSION G. H. Bournc. That is an interesting experiment which would be well worth doing. N. J. Pirie, The importance of distinguishing between the age of a cell and the age of a tissue is well illustrated by the tobacco plant. The cells in most of the Icaves of a plant a foot high arc of comparable age ·SOME ENDOCRINE ASPECTS OF AGEING Ву G. I. M. SWYER Consultant Endocrinologist, Department of Obstetrics, University College Hospital, London, W.C.I AGEING is not unnaturally linked with the idea of rejuvenation, and rejuvenation with the sex glands, since loss of gonadal function may be one of the more outstanding general characteristics of ageing It is of course many years now since the idea was first mooted of bringing about rejuvenation by means of gonadal extracts, trans- HTC, na na-ntinner and it is cerit may be of some value to review the impact of ageing on the activity of these endocrine glands. The gonads Both the ovary and the testis have two distinct functions; to The rongdal ... 1 d. Ada Amator proved necessary in order to explain certain facts of testicular physiology and pathology). In the testis, androgen secretion is 1 ·46 Discussion T were degenerate. Cytoplasmic structure undergoes a series of changes during mitosis, which is most obvious in differentiated cells in which the mitochondria and Golgi apparatus are confined to certain regions of the interphase 11. -...L. -- *) their original form and : Golgi apparatus is reconisible changes, there arc #ha mantne i ·Some Endocrine Aspects of Ageing 49 It must, however, be emphasized that postmenopausal women do not generally show evidence of extreme oestrogen deprivation (such as may be found, for example, in Simmonds' disease, the panen of all the endocrine glands). the adrenal he latter may I. intelligible explanation of the loss of function with increasug age, ternarin and to thp nut- 1 به باد. در وراء to enjoy normal coitus, persists unimpaired in many postmenopausal women Clearly the endocrine aspect of sexual ageing in women may be quite independent of the psychic aspect. - muat different J.-- many authentic examples of men in the eighties producing tertile semen and begetting offspring. Nevertheless, the testis does show evidence of ageing, though it appears to partake of the more general degenerative process which affects the rest of the body rather than of the quite specific process occurring in the ovary. The decline in excretion of 17-ketosteroids with increasing age, to which more detailed reference will be made later, points to decreasing activity of the Leydig cells Actual observations of these in testis sections do not show any obvious decrease in numbers in age. Doubts have been entertained regarding the existence of a male flimorferir hut it msyrafelv, ha ann.1. 12. tion of males do undergo a phase of waning testicular function and ·48 Swyer Engel, 1947 and by del Castillo, Trabucco and de la Balze, 1947) Toth **4UJIUA LIHVIS Much Tullow this and produce the corpus luteum. Furthermore, oogenesis and spermatogenesis show fundamental differences in so far as the former appears to be a wholly foetal process while the latter occurs only in sexually mature males. The actual production of oocytes takes place in the foetal ovary, under what stimulus is not known, and at birth the ovaries together con. tain something between 200,000 and 400,000 oocytes. A substantial proportion of these are destroyed by atresia between birth and puberty. Thereafter, once menstrual function has become established, during each cycle one (or and are expelled from the ovar: destruction of some 20-30 other associated with them undergoing abortive development during the follicular or proliferative phase of the cycle, and arresia during the progestational phase when the ripe follicle has become a corpus luteum. In this way, there is a continual loss of follicles until eventually the stage is reached when few or none semain. Perhaps 400 will have produced eggs, and nearly a thousand times as many will have served the purpose, not of producing gametes but of secreting oestrogens, since there is little doubt that it is from the follicles developing during the follicular phase (as well as from the corpus luteum, and perhaps from follicles undergoing atresia) that ovarian oestrogens are derived. When all the follicles have been used up, it is clear that the ovary is no longer able to secrete oestrogen-or at any rate, not in the way it was formerly abic to do so. īt is this physiologically-determined ovarian insuficiency which is responsible for the cessation, cither gradual or abrupt, of menstrual cycles which constitutes imaçleric. After the hen conceived oestrogen therapy for climacteric symptoms. The anterior lobe of the pituitary gland is also fully effective and, because the decreased production of ovarian Oestrogens has reduced their inhibitory effect upon it, increased secretion of pituitary trophic hormones, especially gonadotrophins, is the consequence. The thyrotrophic and adrenocorticotrophic hormones find responsive target organs and, so it is supposed, these glands may become more or less hyperactive. It is to ihe combination of lowered oestrogen levels and altered thyroid and adrenocortical function that the symptoms commonly experienced by climacteric women are usually ascribed.

·51 Some Endocrine Aspects of Ageing net think non hinhor in men inan 11 win ang UI VULL The ratio of androgens to oestrogens is higher for men than for women at all decades until the ninth. The output of neutral reducing lipids, which reflects the production of corticosteroids, is on the average higher for men than for women at all ages, and varies but little with age In contrast, the nonketonic steroids, a mixture of substances of doubtful origin, part 1 S.clvius ut ledse much less markedly with increasing age in both sexes. The 11-oxyetiocholanolones decrease least of all; these substances derive chiefly from hydrocortisone and its metabolites Steroidogenesis and ageing. The outstanding fact, referred to above, is that with advancing age the vrinary output of corticosteroids changes very little while that of 11-deoxy-17-ketosteroids ·50 Swyer may in consequence experience symptoms of the same genera! female, usually between the ages of 55 and 65. The first to produce scientific evidence indicating the existence of a male climacteric were Heller and Myers (1944) who found that whereas in 15 men with psychoneuroses or psychogenic impotence the urinary gonado. trophin excretion was normal, in 23 men whom they considered to be suffering from the male climacteric the titre was uncquivocably higher. Moreover, testicular biopsies on 8 of these men revealed a reduction in the size and activity of the scminiferous tubules, together with a reduction in the size and number of the Leydig cells, in 5. cases; and in the remaining 3 hyaline degeneration of the histological characteristics. According to Howard et al. (1950), the climacteric can be divided into a compensated and a decompensated stage. In the former there is a tendency to decreased production of gonadal hormoncs, which is met by over-production of pituitary gonadotrophin so that gonadal function remains essentially intact. In the decompensated stage, this tendency to gonadal failure is not counterbalanced, in spite of increased gonadotrophin, and so gonadal failure becomes clinically demonstrable. In the female, the compensated stage lasts only a very short time, but in the male, on the other hand, it is the decompensated stage which is seldom encountered. They therefore con sidered their patients with the male climacteric whose testicular biopsies appeared normal, in spite of increascd gonadotrophin titres, still to be in the compensated stage. The adrenal glands: changes in steroid metabolism in agcing men and women The most deta" ageing men and measured the steroids, rcducing neutral lipids (for corticostcroids), androgens and oestrogens in a group of 297 men and 320 women, all considered to be normal and healthy. It is possible only to summarize their findings here. Ocstrogens. In men, the output of oestrogens remains relatively constant with increasing age; in women, on the other hand, thic output declines between the ages of 40 and 60 ycars, reaching a level somewhat below that of men, and thercafter remaining constant. Or the separate oestrogen fractions, ocstronc and oestradiol ·Some Endocrine Aspects of Ageing 53 result of which ibe falio of androsterone to etiocholanolone derived from the reduction of testosterone is increased, or, as a further possibility, that there is increased conversion of etiocholanolone to etiocholanolone-3x, 176-diol. An exercise test demonstrated a significant improvement in muscular strength in 10 of the men, which was maintained to a lesser degree for at least four and a half months after discontinuation of the treatment. On the other hand, there was no change in the psychological status, neuromuscular co-ordination or encephalograms of the subjects-nor were there any untoward effects. LILI U wills. References del Castillo, E B, Trabucco, A and de la Balze, F A. 1947. J. Clin. Endocrin 7,493 Engel, E.T. 1947 Urol, 57, 789, Engel. ET 1955 Recent Progr Hormone Res, 11, 291. Freeman, R, Parsons, O A, Feffer, MH, Phillips, L , Daneman, E. A, Elmadjian, F, Bloch, E, Dorfman, R1, and Pipcus, G. 1956 1. clir. Endocnn, 16,779 Fleller, C G and Myers, G B 194 J Amer med Asr 126 477 Ilow DD J chin. Cr 1955 I tu, 2, 1, 1353 DISCUSSION B Hamilton The studies by Pincus and his associates extend and confirm much previous work by other in a .. chromatographic 1 ne another ·52 Swyer decreases markediy. This decrease is most probably due to a decline in the secretion of precursor hormones. Now the principal source of neutral steroid hormones appears to be cholesterol, and the two main pathways of its conversion are: (1) splitting of the side chain at carbon 20, leading to the production of As-pregnenolone, which is the prime precursor of the C-21 steroids; this process is stimulated by ACTH (adrenocorticotrophic hormone), whereas the subsequent reactions by which As-pregnenolone is converted into hormonal end-products occur independently of ACTH, as do those of the minor pathway to C-21 steroids which does not involve cholesterol; and (2) splitting of the side-chain at carbon 17, Icading to the production of dehydroepiandrosterone, which is the primo precursor of the C-19 steroids; it is not known whether there is any pituitary trophic influence on dehydroepiandrosterone production. The fact that corticosteroid production is well maintained with advancing years may be taken to imply that the reactions involving breakdown of cholesterol to As-pregnenolonc, as well as all of the enzymatic reactions leading to the conversion of the latter to hydrocortisone, remain unimpaired. The decline in androgen synthesis implies that the ageing adrenal cortex becomes less able to effect rupture of the cholesterol side chain at carbon 17, since this is the initial step in the production of the C-19 steroids of which the androgens form a part. Studies of the steroid excretion patterns of ageing individuals given steroid supplements indicate that the capacity to convert these hormonal steroids to characteristic metabolics remains cssentially unchanged This is confirmatory of the hypothesis that the altcrations in steroid output with age are primarily due to changes in steroid production and not in the subsequent metabolism of these hormones--with certain reservations mentioned below. In their most recent report, Pincus and his colleagues (Freeman er al, 1956) made investigations on a group of 14 men, aged 70 to 91, who received daily for five months a steroid mixture composed of testosterone, adrenosterone, hydrocortisone acctate and corticosterone in amounts which, on the basis of previous calcula. tions, were expected to bring up the average level of blood steroids to those found in young men aged 20 to 40. This trcatment had no cffect upon the serum and urinary concentrations of inorganic ions, upon the blood cosinoplul count or upon the excretion of creatinine. The total 17-.etostcroid excretion rose from an average of 4.5 to 17•1 mg. per 24 hours, was maintained at this level throughout treatment, and declined to pre-trcaiment levels on cessation of therapy, Although the excretion of 11-oxygenated steroids agreed well with the theoretical values, that of 11-deoxy-17-4 ctosteroids differed from M

·DEMOGRAPHIC ASPECTS OF AGEING
Ву
B. BENJAMIN
General Register Office, London, IV.C.2
Tur title of the year mh.-.-
juuluitenlage.
A few simple facis may put matters in perspective:
(1) As yet (an important reservation) the increase in the pro
martinn af all..
129 In the first half of this one...
increased only lead
juliu Hell surviving lo their 70th birthday
cent. The
-4
0.80 years
of course,
The ageing of populations
It will be advantageous to consider first the changes in the age
structure of the population that have taken place in recent decades,
since these changes have given rise to social and economic problems
which have impressed themselves oa the public conscience to the
extent of ctciting interest in the welfare of the elderly person as an
individual. It is doubtful whether there would be the same interest
that there is 10-day in the process of atrine - -
The rahlon,
any ulcs ta 1950-S2 nith that in 1901-10.
...coring comparison of mortauty in England

·54
Discussion
something over fifty surgically-produced healthy eunuchs, 19 10 70 year
of age, and in a comparable series of intact men. There was no evidena
of compensatory increase in adrenocortical function after named
so that these subjects appear to p
plicated by testicular secretions.
which in man arc chiefly metaboli
significantly with age in either caste
for 17. Latent

·57 Demographic Aspects of Ageing Changes in fertility 1.L.L. L'11 --- Change altet Oytors 5 yeert 15 years M 80+ M 60 40- 20- Changt after 55 years 9$ years 35 YO 60- 20- 0 40000 10000 40000 40000 O 40000 40000 Distribution per million persons FIO 2. Change id pyramid following fall in births the hate nfil. udny when the pyramid is wholly based on the changed birth intake its original shape is restored This 15 important, viz., that the effect on age structure of a decline in births is immediate; agetag is prolonged but the change is nevertheless not permanent. Changes in mortality A change in mortality will increase the size of than .. which deathe son با اداره ·56 Benjamin The population pyramid It is useful to illustrate the age structure of a population by means of a pyramid (see fig. 1) in which numbers in successive age groups are represented by the areas of horizontal strips placed on top of each other with the youngest at the base and the oldest at the top (each strip is split into left and righthand portions proportionate to the numbers in cach sex.) They form a pyramid because as a result ENGLAND and WALES 1951 BAAZIL 1050 Femalt Males Females 30. Malas 70 60 50 Age group 30 20- 10-1 40000 O 40000 0000 40000 80000 40000 o Distribution per million persons FIO 1.- Population Pyramids of deaths the numbers remaining in successive age groups become smaller and smaller until a point is reached at which there are no survivors and this is the peak of the pyramid The proportion of older people in the population, say thosc aged 60 and over, is represented by the part of the total area of the pyramid which is at the top above the strip which begins at age 60 (dark hatching of fig. 1). In a country with very heavy, mortality generations, the youngest or most recent being at the bottom.

·Demographic Aspects of Ageing 59 It will be seen that up to the decade 1901-1910 births were increasing in numbers. The pyramid was broadening at its base (fig. 4). The reverse process of fig. 2 was taking place The popula. tion structure was becoming youthful. In 1911 a stable population 1915 JD95 Malts 30+ Females Fumolts Males 70- 60- 50-4 40-2 30 20-2 Age frou 1931 1951 8074 Male Femeter Males Females 70- 60- 50- 30- 20- 10- O. 40000 O 40000 4000 Orntribution per million persons 400OO FIC 4-England and Wales Actual population pyramids, 1891-1951 sustained by constant births and subject to constant mortality "normal" population-would have had 104 per cent of persons aged 65 and over. The proportion k'as actually 5-2 per cent Thus when the fall in births began to takt place, the population was abnormally young and essaſ biriks had remained constant it would have had to grow up".

·58 Benjamin reduction is only at younger ages this will increase the slope of the sides of the lower part of the pyramid but will not affect the top until sufficient time has elapsed for the increased survivors at younger ages to reach the older age groups. Fig. 3 shows the shape of a Change after O years 5 years 15 years 80 M F N 60 40- 20- Age group 35 years, Change alter $5 years M F 95 years BO+ M M 60- 40- 20- 6 40000 40000 O 40000 400OO 0 40000 40000 Distribution per million perions F1o. 3.-Change in pyramid following fall in mortality typical pyramid S, 15, 35, 55 and 95 years after a 50 per cent reduc, though It will The actual changes in England and Wales The changes that have been taking place in the age structure of the population of England and Wales lave been in fact a mixture of the kinds of changes depicted in figs. 2 and 3. Live births in England and Wales in successive decades from 1841 were: 1841-1850 5,488,736 1891-1900 9,155,153 1851-1860 6,471,650 1901-1910 9,298,209 1861-1870 7,500,096 1911-1920 8,096,222 1871-1880 8,588,782 1921-1930 7,129,070 1881-1890 8,890,238 1931-1940 6,064,516 ·Demographic Aspects of Ageing 61 Up to the present therefore the total fertility changes have made a much greater contribution to the increase in the proportion of older people in the population, than has the decline in mortality. The ultimate effect of the changes Thin...71.2.1-1.1. . Arrosdino in the most perant neniantın hand Uve! There will be some changes at younger ages, though these will be comparatively small. Over the next twenty years the population h*** ,- 16- Milu 1913 and 1995 the percentagarna grown up" and has attained comparative stability in its age structure. or ruduuu llas Dependency and economic activity Older persons who have retired from employment have always consumed goods and services, whether purchased hv thaisavings, by relatives or An incre3sc in numbers which is new but it does great importance in tol, av v ww. AJI WA ..

·60 Benjamin This process of " growing up" was accentuated by the declinc in births. The base of the pyramid became narrower and narrower, and a bulge was created which has now moved up to the higher age groups (fig. 4). If births remain relatively constant the bulge will cease to have any appreciable effect on the proportion of older people in the population by the end of the present century. Side by side with these changes mortality has been stcadily declining especially at younger ages at which the conquest of infectious disease has been most effective. At most ages there have been considerable reductions in mortality since 1910. At younger agcs there has been an acceleration in thic improvement in survival rates in the last twenty or thirty years. The effect of this reduction in mortality has been to increase the steepness of the sides of the population pyramid up to quite advanced ages, i.e. to make it run up to a point less rapidly than it would otherwise have done. The full effect of this change will not be felt intilharamannrnrin 1.1.1. ny century (after the effect of the past decline in fertility has largely disappeared). It appears therefore that the temporary ageing of the population structure caused by fertility changes has only just reached its full extent and has not yet spent itself while the permanent ageing duc to mortality improvement has yet to make its full impact. It may be estimated that if mortality had remained constant at the level of 1910-12 the proportion of the population aged 65 and over at 1951, in England and Wales, would havc been 9 7 per cent, com pared with an actual proportion of 11.0 per cent. It'annual births had remained constant at thc level of 1901-10 the population in 1951 would have numbered 51.5 millions (instead of an actual population of 43.8) of which 9.4 per cent would have been aged 65 and over. On the other hand we have alrcady scen that the 1911 population structure was already abnormally youthful as a result of carlier high fertility; this means that even if both mortality and fertility had remained unchanged the proportion aged 65 or more would liave increased from 5.2 to 8.1 per cent in 1951. We may set out these changes as follows: Per cent 65 and over in 1911 5.2 Increase due to abnormal structure in 1911 dic. due to the prior rise in births) Increasc due to fall in births since 1911 Increase due to fall in deaths since 1911 +1.3 +2.9 -1.6 110 Per cent 65 and over in 1951 ... 11.0 ·Demographic Aspects of Ageing 63 cquated, a point on which it is difficult to give a clear answer. In 1995 children and usoccupied women will be fewer and workers future depend. The ageing of individuals There are difficulties in the way of extending the working life. Although mortality has been considerably reduced to the extent that the expectations of life at age 65 on the England and Wales mortalt ainsi --A. - in -1.. 11 3 ani vitality elemento de arrest on imply the the relentless process of degeneration tbough doubtless raised standards of health have generally retarded thus process. Wales during ill be seen that mortality is increasing quite steeply even before age 60 and that : wuu II SL VUU Further Sidlistics supplied by the Ministry of Pensions and National Issurance show that the proportion of the insured male population who were sick on Sth June, 1954, and had been sick for more than three months sose from 1.73 per cent at ages 45-49 to 2.73 per cent at ages 50-SH, and at individual higher ages the percentages were: 433 60 6 64 461 61- 5-30 7-88 62- 8.81 5:48 63 10-22 691 $S $6 $7- 38- $9- ·62 Benjamin Subject to some reservations we may consider as elements of the dependent section of the population (1) children under ngc 15 (2) non-gainfully occupied housewives, etc. (3) persons who have attained the minimum retirement ages (for National Insurance purposes) of 65 (nien) or 60 (women). The balance may be regarded as the supporting rantin proposed to estimate thc in 1975 and 1995 by takin -59. We then obtain the figures shown in the tabic below. Table I.-The economic pressurc of the dependent population in England and Wales, 1901-1955 (numbers in thousands). cols Chil Non Pont- Total dren gain. SIONpopu- underfully able Ratio 10 (6) of Year lation 14 (up occupied class Romainall 10 females der Col. Col. Col. To. ages 1931) 14-59 malcs (3) (+) (5) ial IS ur 10 65+ of (1951-) (1931) females 15-59 60+ 3,4 (1951-) (5) (6) (7) (8) (9) (10) 1901 32528) 9878 6565 1998 14087.70 47.14 (1-31 1921 37887 9772 8188 2972 16955-58 -48-18 1.24 39952 8909 8521 3842 18680.48.46.211.15 1951 43745 9733 8376 5990 19646.50 -43 -301-23 19751 463641 9219 8149 8462 20534 45 40 41 1.26 19951 46328) 8885 8106 8742 20595-43.39.42 1.24 and S (1) 1931 · Based on the population projection referred to on p 39. Catraentinin require the same relative amount of food and services as an adult) while the dependency of adult women las hecn a stabic clement.

·Demographic Aspects of Ageing 63 equated, a point on which it is difficult to give a clear answer. In 1995 children and unoccupied women will be fewer and workers slightly more numerous, on the assumption of the population projection. The total national dependency will not be much greater in 1995 than in 1951. 1. A., tuture depend. The ageing of individuals There are difñculties in the way of extending the working life. duced-to the extent England and Wales 15.0; compared with 113 and 13.1 in 1930-32-it is not easy to interpret this increased vitality in terms of increased capacity to work. Postponement of death in an elderly person by improved medical care does not imply the arrest of the relentless process of degeneration though doubtless raised standards of health have generally retarded this process. We are brought face in farm with the cond... Wales during ill be seen that 13 acressing quite steeply even before age 60 and that aller that are These figures provide DO 1 inment Actuary on the National insurance Act 1946 (1956) indicates that weeks of sickness benefit per annum per employed male in 1949-52 rose from 1.64 at 40-44 10 2-97 at 50-54, 417 at 55-59 and 6-11 at 60-64. Further statistics supplied by the Ministry of Pensions and National Insurance show that the proportion of the fasured male population Whouere sick on Sth Juns, 1954, and had been sick for more than three months rose from 1.73 per cent at ages 45-49 to 2-73 per cent at ages SD-54, and at individual higher ages the percentages were: SS- 4 33 60 6.64 S6 4 61 61- 7.88 57- 5:30 62- 8.81 58- 5.48 63 $9- 10-22 6-S1 ·62 Benjamin Subject to some reservations we may consider as clements of the dependent section of the population (1) children under age 15 (2) non-gainfully occupied houscwives, etc. (3) persons who haic attained the minimum retirement ages (for National Insurance purposes) of 65 (men) or 60 (women). The balance may be regarded as the supporting section of the population. It is proposed to estimate the non-gainfully occupied housewives, etc., in 1975 and 1995 by taking 60 per cent of the femalc population 15-59. We then obtain the figures shown in the table below. TADLEI.-The economic pressure of the dependent population in England and Wales, 1901-1955 (numbers in thousands). Chil Non Pen- Total dron gain SIONpopu- under fully able Ratio to (6) of Year lation 14 (up occupied class Romainall 10 females i.c. der Col. Col Coi. Toages 1931) 14-59 males (3) (4) (5) tal 15 65+ or (1951-) (1931) females cols 15-59 60+ 3,4 (1951-) and 5 (1) (3) (5) (6) (7) (8) (9) (10) up to 4) 1901 32528 9878 1921 378871 9772 1931 39952 8909 1951 43745 9733 1975' 46364 9219 19951 46328) 8885 6565 8188 8521 8376 8149 8106 1998 2972 3842 5990 8462 8742 14087 70-47.14 1.31 16955-58-48.181.24 18680-48.46.211.15 19646-50-43 -30 1.23 20534-45-40-1 1.26 20595-43.3942 1:24 1 Based on the population projection referred to on n. 59. -- require the same relative amount of food and services as an adult) while the dependency of adult womon has been a stable clement. For the future it appears that pensioner dependency will in the next forty years rise by some 40 per cent but almost all of this rise will be offset by a fall in the dependency of children and unoccupied women in so far as the two kinds of dependency arc capable of bcing ·65 Demographic Aspects of Ageing d. anoredricka tha Weich, Ivanu ??. Clearly the problem of invalidity at ages even younger than the hardier members will face a growing burden of chronic invalidity arising from the sheer growth in numbers of older persons outstripping the slower improvement in their average Vitality, On the other hand surveys of the aged population have indicated that infirmity is more quickly developed and more passively accepted in conditions of staggation and boredom and is more effectively resisted and prevented by interest and occupation. -- The extent of employment Tharipada of we be; C. CH C tunel ui Nauonal Insurance was to impose a virtually compulsory retirement age of 65 upon a large proportion of workers, the proportions of men gainfully occupied at older ages were as follows: Per cent of males at each age, Age gainfully occupled 55-59 95-0 60-64 87.5 65-69 47.2 70-74 27-4 75 and over 12.6 At the 1921 Census whea there was some cconomic depression but no widespread system of contributory pensions to in vence

·64
Benjamin
.12-
10
rates
08-
Crude data
Cruct
1
.04
02-
30
40
50
60
70
30
Age
nas-Crude death rates for England and Wales, 1950-52 males

·No text on this page.

·64
Benjamin
The proportion begins to rise rapidly after age 60 and even before
age 65 more than onc-tenth of insured men are in poor cnough shape
to have been on sickness bencfit for more than three months.
.12
10-
.084
Crude death rates
.06
.04
02-
O
30
40
SO
1
60
70
Age
Fo. 5.-Crude death rates for England and Wales, 1950-52 males

·Demographic Aspects of Ageing 67 References 101 Practitioners' Records Government Actuary, 1956 National Insurance Act, 1946, Sth Interim Report, HC 274. DISCUSSION R. A. W Cnca cho sik: curve of d the curves Most dem does not t. introduce Wuulu wula uuierent theaning. B Benjamin The National Lafe Table for 1950-57 is under na- N. W. Pirie If a medical board is considered competent to judge whether a scientist is fit to take in a ich in the ans. may greatl decide wh does not should all As a further example of a man heino resund there 10 Sur Colds in ALLA B Benjamin There is a case for saying that old people should have the opportunity to consider their owa" merits"; taking medical advice but not having it imposed upon them. N. W. Prie. Is the increase in the proportion of women who get married a consequence of a change in the sex ratio or of the progressive removal of the disabilities from which married women have suffered in jobs such as teaching or the civil service?

·66 Benjamin retirement the proportions employed beyond age 65 were considerably larger, viz.im 55-59 94-0 60-64 887 65-69 79.4 70-74 526 75 and over 27.0 Whether this is evidence of the sustaining info or whether it merely represents the time working through stages of unfit , before contributory pensions were ? ww willicult to judge Thc rcal problem which the statistics do not at present measure is the extent to which the economy of the country fails to match the limited and specialized aptstudes of older workers so equally limited and specialized occupations so that they may make the maximum possible contribution to the national product within their physical capacity and enjoy doing it. There is a great need for rcally scientific and objective information about aptitudesmio this the family doctors may hold the key. Housing and family life There ss one last demograpluc aspect of an ageing population which cannot be left out of account, viz., the family units in which older people lne, especially in relation to the incidence of loncliness, and their housing conditions Tabulauons of the 1951 Census (Onc per cent Sample) show that in Great Britain in that year there wers 2,198 thousand households with married licads age 60 and over and about half of these houscholds, 1,129 thousand, consisted of two persons mostly but not quite all of then married couples living alone. Or 3,558 ilousand unmarned persons cnumerated over the age of 60 about one-quarter, viz. some 901 thousand wesc living alone. There were also somc 625 thousand unmarried heads aged 60 and over of houscholds of only two persons. Finally account must be taken of a considerablc number of unmarried persons aged 60 and over enumerated in non-private households. ic. in hospitals, nursing homes, mental institutions, homics for the aged or infirm, and in farger hotels and boarding house containing at least 10 rooms); these mp3 The present pietuva instirutions and hotels, isley seem likely to grow larger. Ainety-seven percent of all married males aged and over yere enumerain in the status of head (or spouse of head of of houscholu. Singic, widoned end dhoreca ·Demographic Aspects of Ageing 67 References Fry, J. 1952 Brit, med , 2, 249. General Register Office. 1956 Quarterly Return of the Registrar General for England and Wales, 4th Quarter, 1955, No. 428 General Register Office 1956. Studies on Med Pop Suby No. 9. General Practitioners' Records. Government Actuary. 1956 National Insurance Act, 1946, Sth Interim Report, HC 274 DISCUSSION RA M. Case. I should like to raise a noint of terminniame Tha B. Benjamin "The National Life Table for 1950-52 is under construirtinn hy tha finomat LA LA LA N. W. Parte If a medical board is considered competent to iuder whether a crientiet is fit in. ne quells. Uw u the start of the institute that B Benjamin There is a case for saylog that old people should have the opportunity to consider their own" merits"; taking medical advice but not having it imposed upon them. N. W. Prie. Is the increase in the time martied a co removal of t1 jobs such as ·68 Discussion R Roxirmin ! is lirimilsin nas improved the marriage prospects of younger wonen but it is also clear from the persistence of high marriage rates that thesc prospects are being taken advantage of more readily and at younger ages by both sexes. P. Townsend. The two ideas of " dependency" and "support " in old age are fundamental to discussion of the economic "burdea " of old age. in Table I Dr. Benjamia show's past and future trends in the economic pressure of the dependent population. As dcpendents he includes children of school or under school age, non-gainfully occupied females and pcople of pensionable age. The question of the dependent population is a tricky and important subject in the first place, futurc population estimates are continually being revised. During the War for crample Beve population in the 1980s which was estimates for the same years, and the economic problem of the agcd has been conducted on the assumption that a decrcasing number of example, has decreased by a million, and presumably many housewives have taken over the same work, yet why call the latter dependents and not the former? There are many other difficulties in sorting out what onc means by the “dependent " population. The housewife supports her husband so that he can go to work. What I am saying is that most workers arc supported by dependents Old people often support their relatives as much as do young wives their husbands In an investigation carricd out in East London recently two-thirds of grandmothers over the age of 60 xcre found to have the regular carc of at least one grandchild. The grandmother helps her married daughters and sons living in neighbouring strecis just as they help her. In the last twenty years in Britain there has beco an incrcase of over a million in the number of marricu women at work. I believe this increuse is related to the increase in the number of grandmothers in the population The upshot 3 we need to be cuclul about our statemeats of the changing number of dependents in the population and how far old people dogxnd on or support others. B. Benjamin. I quite agree with Mr. Townsend. The statement in my ·Demographic Aspects of Ageing 69 Committee on the Economic and Financial Problems of Provision for Old Age" (1954. Cmd. 9333, H.M.SO) fn.hu Lue whole population Reference has been made elsewhere to the greater survival rate of women but I believe that the general impression is correct that though women fast longer they seem to age more completely while they are dninr A Lall- . 4. ... tal 0. 1 DATE 2- A- O- AGE CONTOU - 2 ta et voros AGE 2 3- 4- THE PRINCIPLE OF ANALYSIS BY ÇOKORT AND CONTOUR Fig 6 ·70 Discussion (i.e. date) and the other in equal intervals of time added to the starting age of the animal. If for simplicity we assume the starting age to be zero also, this arts will be age. It is now obvious that observations relating to the original batch of animals will fall along a diagonal (marked "cohort") of this grid. If is kept under different environmental conditions, we should not regard the record found in a vertical column as a biological statement of the mortality experience of the type of animals used, since cach successivt 1.sules avantavle 10 MeiAl calit auc in olier words, Icy wcie a batch of animals Acpt under different conditions, -- England and Wales in the last century when vieised by cohort. (The figures are drawn from a quinary-quinquennial grouping and the cohorts labelled with the central birth-date of the group contributing to the llo experience described). In order not to overload the figure, cohorts spaced (wenty years apart have been selected The progressive improve ment in mortality experience ss shown, and it is now clear that to estra. polate these curves, which is what must be donc to obtain an expectation of life from this mcthod, would be nothing but guessing. I should the to make clear that I do not claim that one statistical accounting Afiss E A Al. Bradford in considering the supposed financial burden of the aged it as well to remember that, as time goes on, with the con. tnbutory pensions system people will, in effect. he paying their own th. Pensions, as now arranged, are not a charity to the accu ginen ty at benci olent population but a conscnical means of compulsory 23ring for those who cannot, or will not, sare during their best financial period of 31ſc.

·Demographic Aspects of Ageing 33 SOOF -- 1956 + 1891 {$$$ 1900 1700F ALL CAUSES 1500 MOOH 1300 AGE SPECIFIC DEATH RATE PER 1,000 LIVING PER YEAR 1200 MOD NALES 1000 900 1800 100 700 100 400 HUDO 30-0 41200 4001 4100 300 1000 2003 DOO too 800 400 50-65 700 700 AGE 600 $D 40 0 FEMALES 500 4400 10 a 2004 30D 1200 10 - 1100 AGE Fig?

·No text on this page.

·FUNCTIONAL CHANGES WITH AGE IN
RELATION TO THE EMPLOYMENT OF
THE ELDERLY
By
W, HOSSON
Department of Social and Industrial Medicine, Sheffield University
Turnhid ----
was u wollen dnu sixty-bve in the case of men. But the set of
JUIJ
Whilst it may be difficult to define old age as far as the individual
18 concerned, it is sometimes easier to define ageing in relation to the
hennartrap 3
obuous wucie ienus to de cellular atrophy, fairy
infiltration and increased pigmentation. There is an increase in
connective tissue and a decrease in tissue elasticity, particularly in
the skin and blood vessels Bones tend to become decalcified and
calcium to be deposited in other situations, such as arteries, thyroid,
pleura, cartilage, tooth pulp, valves of the heart and scar tissue,
These changes may be partly due to a mantents
1111111
by 21
yariati
in the ciderly. There appears to be a wide range in the resting pulse
fornate a much greater significance

·No text on this page.

·75
Functional Changes with Age
---- in the cecial senses are very important in determining
t, Lichoriones,
men.
?
1
hand, is more commons !
arteriosclerosis of the labyrinth. This can be most distressing,
leading to falls and fractures, and is an important cause of impaired
mobility (Droller and Pemberton, 1953) Visual acuity and the
11. the minimum amount
accuracy, that in the great majority of people phys ULDVUE -
cence in the human lens is reached at the age of fifty years, but it
begins before puberty
Until recent years, we have had little information on the normal
ranges of many of the biochemical variables, and even the values
for younger age-groups are often based on inadequate figures. Thus
serum cholesterol, serum alkaline phosphatase and blood urea levels
are all higher than in younger age groups.
Physical Capacity
full of snags and do not necessarily apply to conditions as found in
occupational situations it is well known that after maturity, the
speed reaction time and strength of skeletal neuromuscula
mech:
asms are decreased in moderately hard physical work there is very
older persons, apart
evere work, however,
with age; the chief

·74 Hobson WIJL rate, and in a no--- rate of 74 wittee of tachycardia. Symptoms a itss conspicuous than in younger persons and minor deviations take on a greater significance. Repair is much slower and there is a narrower marrin is anaemia is much more detrimas The rise in t known, but it is much mort mis becomes pathological. It is clear that many old people can remain perfectly healthy with a raised blood pressure. "Hobson and Pemberton (1955) found, for example, that in a random sample of old people living at home, 43 per cent had a resting diastolic blood pressure of 100 millimetres of mercury or over and the majority of these were in good health. In the central nervous system there are a number of changes which, although in a younger person they would be of clinical significance, appear to be of little importance in the elderly. Thus, muscular weakness, brisk knee jerks, wasting pupils which do not react to light, and loss of vibration sense, can all occur in the absence of any evidence of organic disease Similarly, there are certain mental changes which are characteristic of old age, such as impaired memory for recent events, which may make it difficult to take an accurate history. Apathy and depression have important effects on behaviour. There can be little doubt that an adequate well-balanced dict is an important factor in preserving the health of the clderly Mental factors characteristic of the elderly such as apathy and forgetfulness may adversely influence health by leading to a monotonons and inadequate diet. In addition, atrophic rhoncus tract which can have moet for instance, achlor! over the age of sixty concentration of per spuu activity fall off markedly in later life (Meyer, Spier and Neuwelt, 1940). Recent surveys have established the high incidence of chronic atrophic gastritis over the Enge of fifty years. It is well known that dyspepsia and constipation are common. These various factors are no doubt responsible for some of the wasting or malnutrition that occurs in old age, or, in evere cases, for deficiency diseases such as scurvy and anacmia. Changes in the skeletal system can have an enormous eſſect upon person's physical capacity although they might be quite unportant as a danger to life. Examples of these are arthritis and fects of the feet, both very common. Rheumatoid arthritis, for ample, limits greatly the skilled work that can be performed by - hands and is a great disability to a musician or typist or to the Eisewife. Osteoarthritis and spondylitis of the spine are both very Spling deformities for a labourer. The tendency to decalcification particular danger when falls occur. -, all the

·Functional Changes with Age
77
.-.-.t came eyneriments of a rather
entrance and administered again thirty years later suuweu lui sures
are on the whole higher on the re-test.
It would appear that although many age changes are continuous
Seventy,
There is a great need for further research in this field and we
require more information on the actual occupational capacity of
different age groups
The selective process which weeds out the
more unfit with increasing age, complicates studies in thus field and
indicates a need for longitudinal follow-up studies of groups of
individuals in younger age-groups.
Chronic Sickness in Old Age
t
- wou praviugd, un swast

·76 Hobson and are more marked. There is a similar decrease in dexterity. Older men who have had mechanical training appear to be able to maintain the speed rates of young adults (Miles, 1954). This lends experimental proof to the well-known observation that experience and practice can counteract the increasing disabilities of old age. Smith (1938) made a study of men of different age-groups working under conditions similar to those found in factories and he confirmed the observations of Robinson that in short periods, or with moderate work, the performance of the elderly was comparable to those of the younger age-groups. When, however, the conditions became arduous, there was a definite decrease in the ability to perform highspecd manual work. In all age-groups, however, there are great variations in individual ability, so that some of the older workers were able to better the performance of some of the younger workers. This is an important consideration and emphasizes the principle that individual differences should be taken into account whenever the capacity of elderly persons is being considered. Especially important in old persons is accident proneness. De Silva (1938) found that many of the components involved in the driving of a car showed a steady deterioration over the age of thirty years but the mileage driven per fatality showed an improvement with increasing age, at any rate up to the age of fifty years Vernon, Bedford and Warner (1928, 1931), in their studies on the accident rate in coal miners, found a decrease in frequency up to the age of fifty years and that increasing carc and experience can counteract the decreasing performance which might be predicted on the basis of physiological factors alone. The figures for absenteeism are of interest in thus respect but the results as one would expect are conflicting since they are biased by the fact that only those able to maintain good attendance records remain employed Intellectual Changes with Age A considerable amount of work has been carried out on the relation between intelligence and age and changes are found similar to those noted in sensory and motor efficiency, particularly where speed is concerned. This decrease in the score achieved in the intelligence test takes place near the age of fifty years. Again there are wide individual differences in every age-group. The smoothed curves indicating the decrease with age in intelligence test scores take the form of a parabola, with a rapid rise up to the age of filteen years, reaching a peak about the age of twenty years, and a gradual fall after the age of fifty years, with a more rapid decline after the age of seventy years The ability to learn depends largely upon the intelligence, so that memory function, ability to learn new tasks and tasks involving the relinquishing of old habits are found to be more difficult for old ·Functional Changes with Age 79 * One thing is certain; ry broadest generalizans are so very diverse ich in their capabilities, search in Tuninn advising on the employment ol lue crucny, References Bloomfield, A L and Polland, W S. 1933 Gastric Anacidity. Its Relation to Disease New York. De Silva, HR 1938. Sci Mon, N Y., 47, 536 Droller, I1, and Pemberton, J 1953 J Laryng., 67, 689 Fleming, C. 1955 Old Age in the Modern World London, E. & S Livingstone Himsworth, H P and Kerr, RB 1939 Clin Sci , 4, 153 The Health of the Elderly at Home. niern Med , 65, 171, E. J Stieglitz, 3rd edition, London Owens, W A. 1953. Genetic Psychology Monographs, Massachusetts Y 1065 . In 1 . 1931. Rep indus Hilih des, LW LAN Welford, A T 1951 Skill and Age London, Geoffrey Cumberlege, Oxford University Press Weston, H C 1949 Trans Illum Engng Soc , NY, 14, 281-297. DISCUSSION T. Levitt. I was very intrigued to note the high values attained for cholesterol in normal men (409 mg. per cent) and normal women (481 mg. per cent). The values for alkaline phosphatase were similarly high (up WV Hobson The survey was caried out on a random sample of old people over pensionable age living at home, either alone or with spouse Everyone showed some evidence of disease; I consider that any person who did not at this age should be classed as being decidedly abnormal We excluded any cases which were suffering from a disease which was a recognized cause of alterations in the scrum cholesterol or alkaline ·78 Hobson one-third, of all over 65 suffer from impaired physical capacity as a result of chronic disease. Age and Retirement The evidence would seem to lend no support to the idea of fixing sixty-five years of age for retirement from employment rather than, say, seventy. In view of the wide variations in abilities found in the older age groups it might be thought desirable to have some means person from continuing work after the age of sixty-five years, for erample, severe angina, a previous stroke or failure of vision. It is important to remember that those with the best educational and cultural background show the least change with age and any diminution in the powers of critical reasoning may be more than compensated by the knowledge and wisdom gained as a result of experience. One thing is certain, and that is that there is a great need for more refined tests which will measure intellectual capacity in the aged. The present tests do not measure many of the higher mental abilities and tend to discriminate against the elderly, particularly where speed is a factor. They take no account of difliculties due to physical disabilities, for example, deafness, tinnitus, defects of vision, tremor, weakness Although prior to the war the percentage of elderly workers in whole-time employment was falling, it would appear that this trend has now been halted; at any rate in 1954 there were employed in this country, 870,000 men and women over pensionable age and 230,000 over the age of seventy years. Fleming (1955), in a survey ** .duphor charn that ту: 20- power than others. -} worker. The i seventy years, tly raised the Thigher educa- Se of 706 years have been brought out of retirement in order to undertake teaching U 1 years of age. According to Fleming, what is required is, ". an approach which includes one or several of such industrial procedures as a periodic medical check-up of such persons, job analysis and work study applied in this connection, later-age counselling or rctraining, or ·Working Life as a Measure of Ageing 83 work if its health and general conformation allowed; or it might be disposed of for relatively light work on a farm, I am informed that a Corporation borse or a goods horse on the railways employed on heavier work but at a slower pace might, after having been acquired at six years, enjoy an average working life of a further eleven years or more. It is impossible, however, to discuss the subject in brief, because much would depend on the hours and conditions of work. When men become legally entitled to work shorter hours, 50 usually do their horses; and the working lives of horses may then be prolonged by the resulting avoidance of colic, undue fatigue and strained tendons The market value of haar :. ! as hazards of innen animal, Among horses that survive the pectation of life from 6 f twenty-five to thirty y of its reported working ule seems tn mart anma ----- YT With regard to the working lives of timber-hauling elephants, Departmental Instructions for Forest Officers in Burma (1936) state that for purposes of valuation mature animals would be Teckoned ae thone fun cler SS11 - w uli Julests. But wastage due to Disease, accident or overwork would evidently - hala hean a't. 1 + $ f FA I ufficient and is tuse their great development of muscle and the legs to become wuzu ild it may cause the forearms to thin, - ·82 Le Gros Clark shown by younger subjects for heavy work, heat, humidity, long hours, etc. The evidence from these sources may or may not be relevant if we happen to be dealing with ageing subjects who have been for many years exposed to the same conditions. It would be more profitable to examine patiently what factors are applicable to ageing subjects, possibly ideed to ageing subjects alone. In other words, we need a type of job analysis that takes account of the physical and psychological changes we suspect to be characteristic of advancing years. But we have one great advantage. The tasks carricd out by an ageing man or animal are usually " constant" in the sense that they have probably been on the same jobs for most of their working lives. Any decline in their effectiveness or staying power is thus measurable or it can at least be described in objective terms. The results of a study of this kind have always to be reduced to a statistical form, because the tasks undertaken are so varicd and the characteristics of ageing differ so widely from onc subject to another. If we carry our investigations far enough, certain common patterns and common factors should begin to emerge. Though all rescarch of this kind is necessarily laborious, our consolation is that we may discover ways of casing and possibly prolonging the useful working lives of innumerable elderly men, and this would often be of far greater moment to the men themselves than the merc know ledge of an approachung dissolution. Cam more especially interested in the human problem, not only because I am human but because it scems to me that we have reached a stage in our affairs at which all records of the working lives of draught animals are going to become progressively less available to us. Industrial and agricultural undertakings that may formerly have kept reliable records are replacing horses with tractors and motor vans; the old records fave often been long since destroyed, and annual redundancies among horses are making current records, such as they are, virtually useless for estimating the average working life. The literature of the horse is curiously lacking in statistical information on the subject of ageing. For the most part we have to rely on the memories of experienced men. The range of ages up to which a horse may continue on the work for which he had originally been bred or acquired is naturally a fairly wide one; but an age of 10-15 years is commoniy stated to be the average. Ensminger (1951) says that "the market value of the animal increases rather sharply with maturity and then decreases beyond cight years of age. On the other hand, for many purposes horses are quite useful up to twelve years of age or even longer " It appears that in London the railway yards would normally have been acquiring horses at about six years of age; and the medium-built trotting horse used in the light parcel vans would then have been expected to remain on the job for an average of six further years or maybe less. It might then be transferred to slower and possibly heavier ·Working Life as a Measure of Ageing 85 of men aged 60-64 in various large occupational groups who recorded on their census forms that they were by that age already in retirement, ran as follows: TABLE I.--Percentages of Men aged 60-64 who had already retired from the Occupations in which they are Classified, Percentage Occupation already in retirement Building Workers: (Bricklayers, Plasterers, Labourers, etc.) 50 .6 Painters 6.2 14. .. Farm Workers 67 . Textile Workers .. 68 .. Plumbers .. ... 7.1 Workers in Wood: (Cabinet Makers, Carpenters, etc) .. 7-8 .. Dockers ... 7.9 Coal Miners .. 10-1 Though Census figures of this type have to be handled cautiously, it scems probable that most of the men who here said they were in retirement had in fact left or older-11 ·84 Le Gros Clark Williams (1953) records the occasional use of “old crock clephants". (presumably those over 55 years or more) in pushing and lifting logs with the hcad, tusks and trunk from the sand banks or rivers into the main channel. Thus is described by him as "a form of work reserved for penstoned tuskers suffering from old age, deformities or incurable wounds that made them unfit for harness" As for the final cause of death in old age, Evans (1910) says that death may occur suddenly " from long-continued and unobserved disease of the heart. The heart on post-mortenl is sometimes enomously enlarged and may rupture from extreme exertion ". He adds that in old animals degeneration of the blood vessels may predispose to rupture, and that this may be brought about by violent or prolonged exertion. A further description given by Williams (1950) suggests that he considers deterioration of the leart a fairly normal cause of death in aged elephants. "His cheeks are sunken, his teeth worn out. Gathering his daily ration of 600 lbs of green fodder has become too grcat 3 tax on tus energies, and he knows he is losing weight Old age and debility slowly overtake him" In a personal letter Lieut.-Colonel J. H. Williams has written, "I would say that an clephant of so needed particular watching. He was placed in the company of younger anjnals, that could take the biggest strain, the longest haul and the heaviest timber ... If he lost condition at all at that age, it was doubly difficult to put it on again... The first sign of age really affecting the animal's work was loss of power in lus legs. In other words, he looked as if hc must sit down to work rather than stand. He gave the impression that, of his head and his trunk could be used without taxing his strength by clubing the mountain side, then he leid his own. For this reason, al 60 years of age, generally speaking, the animal continued his work on the flat with his tushs, trunk and forehead. I havc known many elephants that continued until they were 70, and they were mostly on that work from 60 to 70 years age. Between 65 and 70 they often showed signs of giddiness, slightly staggering if kept long hours” The ageing man in industry has naturally been more closely studied in recent years than have horses or elephants. But no attempt will here be made to review the literature of the subject. I shall confine myself to a few examples of research procedures that seem to be yielding good practical results. To demonstrate brefly how the statistics of occupation, health and age may be combined for the purpose of rescarch, I will ask what proportions of working mien arc khely to have become more or less incapacitated for further work by their mid-sitties. In most manual occupations men do not retire by choice before they reach the pensionable age of 65. Men have nevertheless to pass into retirement before that age if they are compelled to do so by injury or sickness. According to the 1951 Census (1 per cent sample), the percentages ·Working Life as a Measure of Ageing 87 A study of industrial records usually enables us to arrive at a provisional estimate of the rate of wastage in old age, provided the fecords have been kept with sufficient care, As an example of provisional estimates of this kind, I reproduce a table that was based on small samples of old building workers, bus drivers and bus conductors. The contrasts are suggestive of the significance of the job itself in determining at what comparative ages men have to leave their various occupations. The records were taken without bias from among the records of men who had recently left employment and were traceable to the last moment of service with the undertakings in which they had been employed Some allowances were made as far as possible for the relatively few cases of men who had not been removed solely by reason of old age, sickness or . Lbuilding workers in my sample were employed on maintenance and repairs; and they probably had a better average chance of surviving late on the job than they would have had under the more arduous conditions of constructional work, TABLE II.-Rate of Industrial Survival as affected by Age, 1)) health and Death. 601 63 65 66 67 68 69 70 Age Buildios Workers (320) per cent still on job 0. 10089 83 | 7563 55 4632 Bus Drivers (150) per cent still on job 100 86 78 50 31 21 IS 7 Bus Conductors (150) per cent still on job 100 85 | 80 35 26 23 16 It must be noted, then that the userall traced from the tu 60. In each case the at that age apparenti successive years pri their occur ons by fact the industrial si Whether those who bu ul leired from their customary jobs found some light alternative work, in most cases we ·86 Le Gros Clark year, from the mid-fifties upwards, reaching a level of 8.9 per cent of all the men at risk at the age of 639. While statistical evidson retired before their several years earlier *HIVAN Sickness, it seems yet certain that the ailments of old age increase steadily from the midfifties onwards. By the time they are due for a State pension, at least 10 per cent of the men may probably be reckoned as more or less beyond further work. It would not ha 1 estimate what none. by sea teur, . work; ...u sune concessions in the hours wackou ve tue part they play in a labouring gar northern seek transfers to Soma bitmes indubitably and research It is possible figures. In view of Wuns - ments should be m essential to know? € ated by the I of a working workers on t. losing age. un other onecatinna ves avie 10 continue sa trą 4. to move to other health. Heavines. tempo of work, di in other words, 1 the work that seems vided e IS given opportunities iui adjusting the mode and timing of his work progressively to his age, there is probably kattic reason for supposing that an experienced healthy old labourer could not accommodate himself in comfort 10 most of the strains imposed by any hcavy lining, excavating, etc, he has to undertake But Belbin does not mention that the various hazards, emergencira antenthat a man mav AM "S 1 l was be hran. duration than paper " Demos ·Working Life as a Measure of Ageing A study of industrial records usually enables us to arrive at a provisional estimate of the rate of wastage in old age, provided the records have been kept with sufficient care. As an example of provisional estimates of this kind, I reproduce a table that was based on small samples of old building workers, bus drivers and bus conductors The contrasts are suggestive of the significance of the job itself in determining at what comparative ages men have to leave their various occupations The records were taken without bias from among the records of men who had recently left employmeat and were traceable to the last moment of service with the undertakings in which they had heen employed Some allowances were made as far as possible for the relatively few cases of men who had not been removed solely by reason of old age, sickness or death. hut in L. wunung workers in my sample were employed on maintenance and repairs; and they probably had a better average chance of surviving late on the job than they would have had under the more arduous conditions of constructional work TABLE II.--Rate of Industrial Survival as affected by Age, Ill health and Death, Age 60 ( 63 65 66 67 68 69 70 Building Workers (320) per cent stin on job 100 | 89 83 7563 55 4632 Bus Drivers (150) per cent still on job 100 86 78 50 31 21 15 7 Bus Conductors (150) per cent still on job . 100 85 80 35 26 23 16 11 It must be noted, then, that the variante all traced from the 60. In each case the at that age apparer successive years their occun sonst fact the industrial Whether those wt customary jobs fou w Lutive work, in most cases we ·88 Le Gros Clark do not know; but a number of them certainly made an effort to obtain further employment. The decline in numbers over the mid-sixties is not invariably, and perhaps not even largely, due to a tradition of retiring at 65 years. In several industries men seem to delay the moment when they go in search of a less arduous job until they have the security of a pension on which to fall back; and they incline thus to procrastinate in spite of increasing strain or disability, Cumulative evidence from a variety of sources suggests that in many occupations at least 20 per cent of the men are compelled by their mid-sixties to moderate or change their form of work if they are to have any prospect of remaining in settled employment. This 20 per cent lies over and above the 10 per cent of men who have probably by that age been forced through chronic ill health into final retirement. The proportion for whom concessions become unavoidable incrcases thereafter roughly with the ages of the men, though in some occupations (es. bus driving or work at a coal face) few allowances could be made for a man's age. What I am suggesting, then, is that the working lives of animals and men offer us a chance of glimpsing, and even in some degrec measuring by a reliable yardstick, the physical changes that in. dubitably characterize old age. Under favourable conditions of care and health working animals could provide us with the better subjects for study, because animals presumably have less regard for conventional ideas about old age and about the proper age of rctircment. But, as I have said, we have possibly come too late in history to use draught horses and hauling elephants for rescarch of this kind. The study of men under industrial conditions will involve us in Work Studies of a very special type, in which we shall have to distinguish what varied factors in the relation between the ageing men and their jobs are making it necessary for the men cither to moderate or to change their form of work. We should have to avoid ready-made theories and presuppositions. The method of research recommends itself, becausc ' in our ignorance of what happens in senescence we should at least be observing men just as old age was undeniably overtaking them References Velbin, X. M. 1955 "Older People and fieavy Work.” Buit. La industr Mied, 12, 311. Renedict, F. G 3936. The Physiology of the Elephant. The Carnegie Institu. tion, Washington. 62. General Register Office 1952 Census 1951 Great Britain, } Per Cent Sample. London; H.M.SO. Tables it, 3 and 11 6. Clark, F. Le Gros. 1954 The Later Working Life in the Bathtung Industry. London; Nuſlield Foundation. Clark, F. Le Gros. 1956. Bus Workers in their Later Ures, London: Nuffield Foundation.

·I
Working Life as a Measure of Ageing 89
Departmental Instructions for Forest Officers in Burma. 1936. 153.
Ensminger. ME 1951 Horse Husbandry The Interstate Printers and
Publishers, Danville, Iletons (Sect on "The Importance of Age")
- Dicapps à treatise on clephants
229 and 256.
einent of Elephants,
ins Given for Retiring
Ltd.; London: 51
Williams, J. H. 1953. Bandoola Rupert Hart-Davis Lid, London: 55
du o
DISCUSSION
W.E. Kershaw. I and my colleagues have for some time been interested
both in the longevity of parasites and of their insect vectors, and in the
--Anaty which may hp termed the “infective potential" of
time proved to be of two types, some being normal and others log-normal
in their distnbution. We are at the moment unable to understand why
this difference should occur and what its significance may be.
TV 11rten in
Thor REA
L. 111!
.
I

·90 Discussion being developed all over India as asylums for cattle which have passed their accepted working life. The second point arises from the discussion on the propriety of a fired retiring age. While from the biological point of view there is much to be said against fixing a retiring age, any form of social insurance would appear to make such fixation essential. We are faced in the tea industry in India with the introduction of a social insurance system involving a statutory provident fund and retrenchment and retirement compensation but since it is at present virtually impossible to terminate any worker's employment, apart from senior executives, I find myself bound to support the fixation of a definite retirement age. While naturally biological factors must be taken into account, the reasons for fixation are not so much biological as financial and economic ·PSYCHOLOGICAL CHANGES WITH AGE: THE PRESENT STATUS OF RESEARCH By ALASTAIR HERON Medical Research Council Group for Research on Occupational Aspects of Ageing, University of Lirerpool It is perhaps important to make it clear from the outset that the perfectly understandable; there are a great many old people these days, most of whom are in need of care, of understanding, and of workable solutions to their difficulties. Nevertheless, here as elsewhere in the biological sciences pure and applied, it is likely that prevention will in the long run prove better than cure; if this be agreed, then it is the process we must study, rather than the endproduct As any organism develops, it changes; as man is a relatively complex organism, the changes will naturally be difficult to assess. More importantly, as the time-span within which these complex VIL Umg i psync allu psychologic changes occurring with advanced age, little agreement exists as to what these changes are of what they mean" The purpose of the present review is to gather together some of the more satisfactory research materal in such a way as to indicate points of departure for fresh enquiries. Beach (1954) has suggested that three generalizations may be made about all aspects of organic development or these the first two are sufficiently familiar to he amusing. "Taunle. C. 1 AU willall out rises a maximum at a particular age and then decreases." The outstanding feature of our present picture of the developmental process is certainly one of falling potentialities, and it might ·92 Heron be tempting to regard Beach's generalization as but a different way of saying just this. There is however the other aspect, allowed for by Beach, but not so often noticed in the general literature on ageing: 2 "decrease in sensitivity to environmental influence may well represent a psychological asset--but only if we are prepared to regard man as more than an input-output system. The outstanding work of Lehman (1953) leaves us in little doubt that, so far as the creative intellectual fields of endeavour arc concerned, both quality and quantity of output reach their peak early in lifcumin almost all fields before the age of 40. But he does note (p. 330) that " as a result of positive transfer the old usually possess greater wisdom and erudition. These are invaluable assets." Wisdom may well be the fruit of the contemplative years which lie beyond the point of “ decreased sensitivity to environmental influences".but by its very nature seems likely to prove resistant to objective measurcment. This being the case, it is only natural that most of the quantitative findings so far presented in the literature, being of a kind dependent on continued interaction between the organism and the environment, should tend to show varying degrees of decline with age. On the available evidence from medical and physiological sources, Lelman (1953, p. 328) is probably justified in stating that "a decline occurs prior io 40 in physical vigour, energy and resist ance to fatigue". Adverse changes with age are also charaçicristic of the two principal distance receptors the eye and the car. For practical purposes it would appear desirable to face the fact, however unpalatable it may be emotionally, that in Lehman's words possibly every human behaviour has its period of prime". This donc, it may be easier to see the objectives for psychological research on the process of ageing as being in the words of Bromley (1956b). " to point the way towards reduced stress and grcater achicvement during the mature and decining years These are "applied objectives ", the approach to them must be made both by the direct route and by the more circuitous path of relatively "pure " caquiry 63 Percepłion Reference has already been made to the cyc and thic car: lcst their pre-eminence be questioned, we may do well to note the judg. meet of Sherrington, as quoted by Adrian (1949). "The distance receptors are the great inaugurators of reaction ... (thcy) integrate the individual not merely because of the wide ramification of thcir arcs to the cllector organs through the lower motor centres, they integrate especially because of their great connections in the lugh cerebral centres. Loss of elasticity in the lens starts in childhood, resulting in a gradusi narrowing of the range of accommodation, whilc acuity ·Psychological Changes with Age 93 for distant objects begins to show decline from about 45 years of age (Crouch, 19;45 Dennis, 1953), Adequate knowledge of changes 10 the perception of depth and of colour is not yet available, but McFarland and Fisher (1955) have shown that complete dark sound stimula "as reflected in decrease in mean maxima and minima pupil diameters, extent of constriction, and response vplarini After det...4...if ... U mus number many may be helped by surgery or by visual So far as hearing is concerned, it is well-established that there is a aids B. LY HUL YOL Quey ulucislova: while it may be possible that the normal dectemental process may be accelerated or its results made more severe by a sustained high-intensity noise in the working environment, it is known that a noisy background sometimes assists the older person to maintain an adequate communication level. Finally, it is worth noting that no studies have yet been located in which both yusion and heating have been studied in the --- dividuals in salns.. been take of increas to which ·92 Heron be tempting to regard Beach's generalization as but a different way of saying just this. There is however the other aspect, allowed for by Beach, but not so often noticed in the general literature on ageing: a "decrease in sensitivity to environmental influence" may well represent a psychological asset-but only if we are prequality and quantity of output reach their peak early in lifemin almost all fields before the age of 40. But he does note (p. 330) that " as a result of positive transfer the old usually possess greater wisdom and erudition. These are invaluable assets." Wisdom may well be the fruit of the contemplative years which lie beyond the point of " decreased sensitivity to environmental influences "-but by its very nature seems likely to prove resistant to objective measurement. This being the case, it is only natural that most of the quantitative findings so far presented in the literature, being a kind dependent on continued interaction between the organism and the environment, should tend to show varying degrees of decline with age. On the available evidence from medical and physiological sources, Lehman (1**. a decline occurs ance to fatigue" of the two principal distance receptors-the eye and the car. For practical purposes it would appear desirable to face the fact, however unpalatable it may be emotionally, that in Lehman's words possibly every human behaviour has its period of prime ". This done, it may be easier to see the objectives for psychological rescarch on the process of ageing as being in the words of Bromley (1956b), " to point the way towards reduced stress and greater achievement during the mature and declining years ". These are "applica objectives"; the approach to them must be made both by the direct route and by the more circuitous path of relatively "pure enquiry << 11 Perception Reference has already been made to the cyc and thic car: lest thcir pre-cminence be questioned, we may do well to note the judg ment of Sherrington, as quoted by Adrian (1949): "The distance receptors are the great inaugurators of reaction (thcy) integrate the individual not merely because of the wide ramification of their arcs to the cffector organs through the lower motor centres; they integrate especially because of their great connections in the high ccrcbral centres." Loss of clasticity in the lens starts in childhood, resulting in a gradual narrowing of the range of accommodation, while acuity ·Psychological Changes with Age 93 for distant objects begins to show decline from about 45 years of age (Crouch, 19; 45 Dennis, 1953) Adequate knowledge of changes 10 the perception of depth and of colour is not yet available, but McFarland and Fisher (1955) have shown that complete dark odontntion in the follor at nettofon ihan sound stimula " as reflected in decrease in mean maxima and minima pupil diameters, extent of constriction, and response velocity". After drawing attention to the need for studies of such variables as states of stress, tension and fatigue, and the effects of various drugs. she adds the nositive not that the idroma ceni nave suthcient visual impairment to interfere with their activities of this number many may be helped by surgery or by visual aids." So far as hearing is concerned, it 15 well-established that there is a progressive hearing loss with age, principally however in the higher frequencies above 2,000 cps. This results in problems of internerenniame - Ma laul yet aueyuussy unleerstood: while it may be possible that the normal decremental process may be accelerated or its results made more severe by a sustained high-intensity noise in the face ment { ·94 Heron Motor Performance Thic development of muscular strength, according to Fisher and Birren (1947)" follows a systematic trend with an increase up to the Jate twenties and a decline, usually at an incrcasing rate, from that time on". Simple reaction time in response to an auditory stimulus tion has yet come to the notice of the writer. Apart from the apparent differences in experimental technique, and the fact that the proportionate increase for Birsen and Botwinick's study is double Thai for Obrist's, the two investigations agrec in providing evidence of a slowing down with age. Birren (1955) elsewhere quotes Rashevshy as his authority for stating that“ in general, the stronger the peripheral stimulus, the shorter the scaction time". The relation of this general observation to age might well repay close experimental examination. Movement time was until recently also regarded as showing a marked increase with age, largely due to an early study by Miles (1931). However, from evidence presented by Leonard (1953), Szafran (1951) and Singleton (1954), consistent with the general findings of Rubin, von Trebra and Sinith (1952), it seems clear that although there is some increase (mainly after 45-50 years of age) it is smal} in relation to that which has been demonstrated for decision making at the critical points in a psychomotor task. This leads us directly to the studies of skillcd performance in relation to age -- 23 importance so far as complex psychomotor shell is concernca. -'... or outgoing action", and of the iwo fatter it is the faslurc in " percoptual organization of the incoming data which is the more serious prob} ml....... in connection ion to the work xplain his results (obtained in two very satisfactory experiments on amming) one must conclude "cither that older persons are reluctant to rely on reduced sensory cues in the performance of a task, or that they need to marshal all possibic sensory data in task performance" As the latter suggestion itself provides an explanation for the former, st is logically to be preferred, and it is consistent with Welford's thcorctical position. Welford himself mestions (1953) the findings of Weston (1949a and b) that “poor lighting, small sizc of detail to be ·Psychological Changes with Age 95 seen, and lack of contrast between objects viewed and their background can lower speed of work between the twenties and the fifties, even when subjects are matched for visual acuity by Snellen charts and Jaeger test types". Improvement in one or other of these respects would of course increase the available sensory data relevant to the task, and this would consequently benefit the older people relatively more than the younger. Welford makes the point (1953) that analogous results might be obtained in an auditory inspection task where a particular sound might be critical. Adolt Learning It is of course but a short step from considerations of sensory and psychomotor efficiency to an examination of our present knowledge about adult learning in relation to age. There are, broadly speaking, five main aspects of this fundamental psychologicaltopic: intellectual ability, short-term retention of new material, long-term remem bering.. problem-solving, and creative thinking. This is not of II UU ULINI ITU LIUNTAA demonstrat and compt arrangemny ditinnenfarin www w USS Undel umed and intimad 1 su ludh at 30 years, it is not Alloun whether a loss in memory ability during this period consists ·96 Heron of a small lpee pynerienrad humant", few." : 16 to the 1 was only halt as great. The evidence concerning long-term remembering is condicting, fargely due to the almost complete absence of longitudinal studies of individuals and to reliance on material obtained from psychiatric subjects. Jones and Kaplan (1945) present a good deal of this conflictiag material before coming to the conclusion that since memory defects are frequently progressive, we are not justified in talking about senile memory as a single condition. The fact remains that memory defects are, perhaps, the most salient psychological symptoms of ageing, both normal and pathological." This seems rather strong for the availablc objective evidence. So far as problem-solving is concerned, Clay (1954) has demonstrated that when time-stress is not present, the performance of older subjects (55+) comparcs well with that of younger subjects (<25) on a simple problem, but as the complexity of the problem is progressively increased, the older subjects become slower and less accurate, and finally in some cases fail to complete the task. Kay (1951) approached the study of problem-solving from an unusual angle by, in elfect, giving his subjects the solution: their task was then to think how to make use of it. He says rightly that this technique does give us some precision which is open to further analysis. By predicting certain types of mistake it is possible to confirm what it is that is holding up a subject's progress". This approach enabled Kay to combine the results obtained in this task with those from a rotc-learning study, leading him to the conclusion that it was reluctance to discard their own ideas which character szed a poor performance both in the learning and in the problem. solving) experiment". The implications of this conclusion for the re-training of older workers must be obvious, and it also suggests the need for fresh examination of the ofl-quoted "rigidity" of older people and the assumption that this is a “personality" featurc Further reference to creative thinking in the ordinary sense covered by the work of Lehman (already quoted) seems unnecessary, but aitempis to tackle the problem directly by a planned study arc so rare that a recent paper by Bromlcy (1956a) is most weicome. He used the Shaw Test, publicized by Howson (1945) and adapted by Dromley himself. It consists of four wooden blocks which can be arranged in different series, according to height, weight, position of a notch, and so on. Bromley concludes from the use of the tes! with 256 men and women, aged 17-82 years, that “ although loss of intellectual efficiency with age does not cntirely account for the decline in quantity and quality of creative output, it does account for the major part ". His mčasure of " intellectual efficiency" is of old age.

·97 Psychological Changes with Age ......le.n.l.re...nhrot. -1:-'; having in large part the connotation of productivity in circumstances where the subject's responses are for all practical purposes not limited by the nature of the task. In view of the work of Howell (1955) previously cited, it would be of great interest to see to what extent variations in "creativity" or " productivity.", as measured by the Shaw Test, can be accounted for in terms of the "hold" and * don't hold" groups of W-B sub-tests. Emotional Stability So far as it is possible to judge from the available literature, our firman 1.1- sudky a great need here for sound research by relatively objective methods. Work Performance We come finally to a consideration of what oras na effects c related there is the orig. pulvllalke is inaintained, but only by means of increased effort. Second, a change of method may enable achieve. ment to be maintained nr even immeund achie studis tasks Alder do m repor Value ww). Ulic of the big concerned is surely th Turinn - Eusk UIT 1741 in thn L. JAILUS about them. Union ·98 Heron leaders, they found, feel older workers are capable workers and are also victimized by prejudices of their own about older workers. tion. Belbin (1955) however examined the commonly-held vicw that older people should be transferred to lighter work, and the implication that heavier work is not suited to older persons. He found that "those occupations which could be recognized as heavy and strenuous tended to have a higher proportion of persons engaged on them between tlic ages of 45 and 60 than did lighter skilled operations in the same industries ". Conclusion 'has been taken That there is be emphasized is that significant progress cannot be achieved without carefullycontrolled longitudinal studies of individuals. 20 PP. References Abranis, A. J. 1955. Discrimination against older workers in various countries." In Old Age in the Modern World. London: Livingstone, 291- 295. Adiran, E.D. 1949. Sensory Integration. Liverpool: Univ. of Liverpool Press, Amholt, F. H. 1955. "Research problems in serontology," J. Geroni., 10, 452-456. Beach, F. A 1954. "The individual from conception to conceptualization." In Patton, R. A. (Ed.) Current Trends in Psychology and the Behmloral Sciences. Pittsburgh: Univ. of Pittsburgh Press, 82-514 Belbin, R. M. 1955. "Older people and heavy work." Brt. J. Incluir. Nied, 12, 309-319. Birtca, J. E. 1955. "Agc changes in speed of simple responses and perception and their significance for complex behaviour." in Old Age in the Modern World. London: Livingstone, 235-247, MTN-in finner it on foot - Dentis, 4. 1 lgt w** tHuU4. School of Aviation Medicine, Project No. 21-0202-0005, Report No. 1. Fisher, M. B. and Birren, J. E 1947. "Age and strength." . arri. Psychol.. 31, 48-497.

·Psychological Changes with Age 99 Gubert, Jeanne G. 1952 Understanding Old Age, New York; Ronald Press Howell, R. 1955 "Sc« differences and educational influences on a mental detenoralion scale" ] Geront, 10, 190-193. Howson, 3 D. 1948. “ Intellectual impairment associated with brain-injured patients as revealed by the Shaw test of abstract thought" Caned J Psychol, 2, 125-133, Tanec Lanni 17) "L...- Kay, R 1951. "Learning of a serial task by different age groups." Quarı .. exp Psychol, 3, 166–183 Kleemercr, RW. 1954 "Age changes in psychomotor capacity and productivity." J. Bus Univ. Chc., 27, 146-155. Kornzweis. A. L. 1954. * Physiological effects of age on the visual process." Sight Say. Rev. 24, 130-138. Kumruck, Lilian $ 1956 "Ageing and pupillary response to light and sound stimull." J. Geront., 11, 38-45, Lehman, H. C. 1953. Age and Achievement. New Jersey: Princeton Uniy. Press, Leonard, J. A 1953 "Advance information in sensori-motor skills" Quart J. exp. Psychol. 5, 141-149. McFarland, R. A. 1956. "The psychological aspects of ageing " Bull N.Y. Acout Med, 32, 14–32. McFarland to Ar... Kubin, R., von Trebra, P. and Smith, K. V. 1952. " Dimensional analysis of molog III Complexity of movement of patient" J. appl. Psychol., 36, 272-276. Singleton, W. T. 1994. "The change of movement timing with age." Brsi, J. Psychol. 45, 166-172 Szafran, J. 1951. "Changes with age and with exclusion of vision in performance at an aiming task." Quart. I exp. Psychol, 3, 111-118 Vincent, D. F. od Age and Test Perfor 1. 23 "Extending the employment of older people." Brit. med. J.,2 1193, Welford, A T. 1955. Problems and methods of further research" in Old Age in the Afodern Borld. London: Livingstone, 333-338 Weston, W. C. 1949. On age and illumination in relation to visual per. formance." Trons. Illum. Enghz. Soc. 14, 281-297. Weston, H. C. 1949 Sigur, Light, and Efficiency. London: Lewis.

·100 Discussion DISCUSSION F. Verzar I admired the excellent lecture of Dr. Heron and should like to underline two points which he raised. First, the importance of experimental psychological studies of the ageing process. He pointed out that there are not only deteriorations but also some well-proved improvements in certain qualities in the aged. The irreversible decrease of elasticity of tendons and skin, the loss of physical strength, etc, are parts of the basic changes in the tissues during life. Our main practical aim in gerontology is, I think, not rejuvenation in the common sense, or prolongation of life beyond its natural limits, but rather to keep the aged in such physical health that they can use what we may summarize as their experience for the benefit of the community. Loss of physical health reduces life expectancy, but increased experience coupled with relative health makes the old person a leader of his group. From such a point of view, experimental psychological research is not only of theoretical but also of the highest practical value. It may be able to show us, not merely in general but also in certain dehnte cases, such as the work of factory workers, medical men, scientific workers, teachers, etc., the particular type of work in which the older int. replace the younger to the advantare borok I fully agree also with the secat Research on ageing should soron f different age hi Two years a started work iung term investigations on the same Hrvlaers from a particular factory, in which they usually work from early youth to old age, arc cxamined individually systematically every one or two years by an aphthalmologise for changes leading to presbyopia, by a medical officer for general health, by a physiologist for pulse wave velocity, etc The first report was given in April 1956, by Dr R. Bruckner at the Basic Symposium on Experimental Research on Ageing. We very much hope that simular research will also be started by other research groups. ولا زووور .

·NUTRITION AND AGEING Ву H. M. SINCLAIR Laboratory of Human Nutrition, University of Oxford latroduction 1'. 4Y clear that the concept of growth here adds anything other than confusion, and whereas becoming older implies mere passage of time, becoming old implies showing signs of old age. An infant as it La--11: L.. ol nutrition. Nutrition before Maturity Maturation is the process of coming to full growth of development, which state is called maturity. There are various criteria of maturity: maximum length, ability to reproduce and the menarche are the three commonest A fully-grown eunuch has reached maturity, a spawning fish has also reached matunty: therefore neither ability to reproduce nor maximum length can be taken as an absolute criterion A great many experiments have thown that ...--- before maturity delays of these facts have bee 1903), for butterflies (Chapman, 1920), for for Daphnia (Ingle, 1 VỊ ƯUI alu Balla, 1931), for caterpillars of Limantria desper (Kopec, 1924), for tadpoles (Kopec, 1928), for the limpel Patella vulgata (Fischer-Piette, 1939), for im ASIL ·102 Sinclair nonton · McCay, Dilley and Crowell, :'), for rats (Jackson, 1937; 147; Riesen, Herbst, Walliker «110 Livenjen, 1941, 'Templeton and Ershoff, 1949; Sherman, Campbell and Regan, 1949), and for cattle (Hansen and Steensberg, 1950). Northrup (1917) for example showed that undernourishment of Drosophila during the larval period prolonged this and increased duration of life from nineteen days to twenty-nine days. Kopec (1924) fed and starved caterpillars on alternate days, and thereby could prolong the duration of the larval stage from about 16 per cent to about 90 per cent of that of control aninals, the nenlenen in hun . (1952) showed that undernourishment of the sessile protozoan Tokophrza infusionum prolonged life whereas overnourishment shortened it. The most careful and extensive work has beca donc by McCay and his associates. For instance, in experiments started in 1930 (McCay, Sperling and Barnes, 1943; McCay, 1952) it was found that rats could be retarded as much as 1,150 days by undernourishment and still resume growth when adequately fed. They Jived longer because of slower development of the clironic diseases that attacked the lungs, kidneys and middle ear, and tumours developed more slowly (as had been earlier shown in mice by Moreschi (1909)). McCay concluded that the type of aliments provided in an adequate basal diet mattered little in relation to lifcspan; the amount of aliments, or number of calories, was the important factor. Is life maturity rate? Ti.. (1912) with tadpoles. The simple explanation that rapid growth shortens life does not scem to be correct: Carlson and Hocizel (1946) found that intermittent fasting prolonged the life-span of rats and retarded the development of mammary tumours, but without influencing the growth rate. McCay's undernourished rats were active, and although their basal metabolic rate was somewhat Jowered their total metabolism was normal. The cvidence is against the cffects being brought about through altered rate of development. The effect of undernourishment is probably mediated through the pituitary. We could suppose that food stimulates the anterior pituitary to produce both gonadotrophic lormonc, so that development takes place, and growth Hormone which allows phospholipids to be synthesized in the body with the aid of essential fatly acids. If these phospholipids are formed, growth occurs; if thcy are not formed, through absence of essential fatty acids or absence of growth hormonc, growth of the body does not occur.

·Nutrition and Ageing 103 Since it is very consistently found amongst lower animals that overbourishment hastens maturity and shortens the life-span whereas undernourishment delays maturity and prolongs life, the same might be true of man. In 1832 Edmonds published his "new theory of the cause producing health and longevity". He believed quand, 1951) Conversely, undertourishment is known to delay -- Unutul TUICA, US WIIULI he lleve lecotus, iniuugn we. Brody (1945) showed that the proportion of life-span used in reaching mntunty it ronctant for hinhne animal LIHIN ...UW wy wou with vitamin B12 and aureomycin, even though these activities make them grow more quickly and mature earlier" (Sinclair, 1951). Even earlier (Sinclair, 1948) I had tried to point out that's inevifficiant thanaki - desirable rate o We can make : otherwise be by djeluilig anterior pituitary Jobe extract; alternatively we can make him heavier and probably taller by superalimentation. There is indeed a tendency amongst nutritionists to regard the child of perfect nutriture as placid, rotund, red faced, and seated in contented contemplation of its folds of flesh. During the past several years there has been a marked increase in the rate of growth of children, although in England and the US the adult malamenta has remained unchanged. It in rate is necessarily advanta. since the long time taken to human genus" This is a ve cussed at the Ciba Symposiur * puu), Illy sorgewbat lonely crusade has been joined by McCance (1953; McCance and Widdowson, 1935) It may be that we should consider as the best diet in regard to aliments that whink .. I!

·104 Sinclair passing almost immediately into a long period of senility would be unfortunate. To some extent McCay's increased longevity was gained at the expense of the period of maturity before scnility was apparent. The whole subject deserves more attention. I have discussed aliments only because little is known about the effects that deficiency or excess of nutrients before maturity has upon senescence. For instance, Fritsch (1953) found that the amount of paptothenic acid in the medium was an important factor in detere mining the life-span of Daphnia; this and similar observations may complicate some of the results obtained with undernourishment. Lansing (1942) found that rotiſers live longer in a medium low in calcium, and he suggests that senescence is caused by an increase in calcium at cell surfaces with lowered permeability and accumulation of toxic metabolites inside cells. Research in the field of nutrients is badly needed. Nutrition after Maturity Whereas most of our information about the cffects that nutrition before maturity has upon senescence is derived from experiments upon lower animals, most of our information about the effects of nutrition after maturity is derived from observations upon man. There is good evidence that overnourishment after maturity increases the incidence of ----- In lower animals the undernourishment of the lary undernourishment of the imago does not and may cven decrease it (Kopck, 1928). However, adult ticks, Dermaccntor variabilis, that have become attached to a host and are feeding freely, die within a few weeks, whereas unattached adults can live for more than two and a half years (Bishopp and Smith, 1938). McCay found that ilic effect of undernourishment upon life-span was much less in rats when it occurred after than when it occurred before maturity (McCay, Maynard, Sperling and Osgood, 1941). It has been known from ancient times that fat mon dic carlicr: Plures crapula quam gladius (Gluttony kills more than the sword). That careful observer Robert Burton may have come cry ncar the truth when he wrote in the Anatomy of Mclancholy. "As a lamp is choaked with a multitude of Oyl, or a little fire with overmuch wood quite extinguished; so is the natural heat with immoderate cating strangled in the body." Certain of those who had indulged immoderately in food and drink, such as Luigi Cornaro (1558) and the Miller of Essex, were driven to temperance by the dread of their former sufferings.

·Nutrition and Ageing 105 Dublin and Marks (1951) and Armstrong, Dublin, Wheatley and Marks (1951). Dublin analysed the mortality of persons who had becn insured as sub-standard risks because of overweight between 1925 and 1934 and who were traced to 1950 It was high, and increased markedly with the degree of overweight. As I have pointed relatively minor disorders that are more frequent in the obese mainly for mechanical reasons; degenerative arthritis in knees, hips and Inomhar enina formirane muss HI HUWWE Luv age or twenty-Nive years, and their decrease thereafter is certainly a criterion of senescence. It appears that appetite does not decrease as much as does muscular activity after this age, and of course there are usually - SULLIULUI !! Duese women and rarer in under nourricharm IL. The most interesting and important of the disorders that are commoner in the obese are the desenerativa renal di 351$. V. occur it increased In Vic 1 vury TUU cardioy I wishiaje unu iis relation to nutrition, some discussion is required. I have put forward elsewhere reasons for believing that a relative deliciency of the essential fatty acids, linoleic and arachidonic, is becoming increasingly, prcvalent in this country as in most other highly civilized countries (Sinclair, 1956a, c, d) These acids are of Course easily destroyed by oxidation, by hydrogenation and even by ·106 Sinclair 11 conjugation of the double bonds as by ultra-violet light. The unnatural" (all-trans or cis-frans) isomers, and isomers with conjugated double bonds act in the body as antagonists of the ordinary required isomers which are all-css. "Unnatural" is not an ideal term because cow's milk and butter contain almost none of the ordinary form of linoleic acid and a relatively large amount of cis-frans linoleic; cod-liver oil contains no ordinary linoleic acid. This may be yet another reason for thinking twice about pouring jugfuls of milk down the throats of children and spoonfuls of cod. liver oil down the throats of infants. Deficiency of essential fatty acids caused by consumprion of diets low in them and containing the "unnatural" isomers produces disorders. High unsaturated fatty acids occur in the body in cholesteryl esters, in butyl alcohol, la glycerophosphatdes (particularly ethanolamic phosphatide) and in cardiolipins (where linoleic acid represents five-sixths of the total fatty acids). These polyethenoid fatty acids include others besides linoleic: Command Cer-Polyethenoid acids occur abundantly in the glycerophosphatides of liver and brain (Klenk and Lindlar, 1955; Klenk and Dreike, 1955), and can be formed from linoleic in presence of vitamin B. (Witten and Holman, 1952) by addition of acetate followed by dehydrogenation (Steinberg, Slaton, Howion and Mead, 1956). This vitamin is not the only one that plays a part in their metabolism vitamin E protects them from oxidation. But much of the vitamin E in our dicts ss destroyed by the so-called Nour improvers; and the content of vifamın B., formerly not high, has decreased considerably since the bread subsidy ended on September 30, 1956. When the essential fatty acids arc absent they may be replaced by oleic acid or saturated fatty acids synthesized in the body; this may also occur if there is a selative excess of saturated faily acids as perhaps on diets nigh sa aliments, or in diabetes mellitus in which large amounts of fat arc metabolized. The essential fatty acids can also be replaced by unusual highly unsaturated fatty acids if thesc are present in relative excess. The unusual compounds so formed do not function properly in the body and therefore can give rise to degenerative disease. For instance, Dr. Basnayake and I found tuo years ago that rats on a fat-free dict esterified cholesteryl with fatty acids synthesized in the body rather than with highly unsaturated fatty acids which the body cannot form, and the unusual cstcr was deposited in the skin; simularly, serum phosphardes mere raised and had an unusually low rodinc number in coronary thrombosis the atheroma might be caused by deposition of an abnormal cholesteryl ester, and the increased coagulability of the blood might be caused by a raised concentration of cthanolamine phosphatide, which is known normally to contain an unusually unsaturated farty acid and which Robinson and Poolc (1956) have shown to increase the coagulability of blood.

·Nutrition and Ageing 107 There are two conditions in infants in which atheroma, commonly regarded as a sign of senescence, is said to occur: progeria and 1.1. L-..-1- AL sensitivity to vitamin D (Sinclair, 1956b); the adult form of this deficiency with adequate dietary calcium and vitamin D might be Reinhani ---- T with senenpart by caused by detective membranes of the cells of the stratum granulosum. It is possible that the alteration in permeability of old cells might be related to imperfection of the lipoprotein polymer. In deficiency of essential fatty acids wide. ULLA duulluudtes in old cells is related to peroxide formation from unsaturated fatty acids. It would be interesting to study these changes in old cells in relation to essential fatty acids. Effects of Senescence on Nutrition Digestion and absorption become impaired in old age. Loss of tecth, diminished saliva, and diminished gastric acid contribute to this. Half a century ago Metchnikaſt thought that senescence was caused by poisons derived from intestinal putrefaction, and heroic measures were taken in the interests of intestinal hvgiene; now we venerate our inte.10.. ygen are less effi cells may be im Requirements may be altered. The increase in body-fat and decrease in muscle that occur with ageing raise two important questions: first, what is the "normal amount of fat and what represents obesity in the elderly? secondly, should the calorie requirements be decreased? From the work of Shock it seems ·108 Sinclair ܕܪܪܪܨܝܬܬ.1.1. eating, and this increase is undesirable. There is a conflict of opinion about calcium requirements of the elderly: osteoporosis is probably more related to failure of protein anabolism than to dietary calcium deficiency. The most important effects of senescence upon nutrition are thosc associated with conditions that are all too often found in old persons: poverty, ignorance and apathy. References Armstrong, D. B., Dublin, L. 1. Wheatley, G. M.. and Marks, H H1, 1981, J. Amer. med. Ass., 147, 3007, Basnayake, V. and Sinclair, H M 1954. J. Physiol. 126.55P Basnayake, v. and Sinclair, H. M 1955. Proc. 2nd Internar. Congr Lipids, Ghent. non impic, Circ., 478 id Harper, M. 1955 Reinhold. n'.L - m. 1710 Amrr ) Ohser nec, 56, 4U Comaro, L. 1558. Trattato della vita sobria Padova: Perchacino Dublin, L. 1. 1930 Int. Biol. 2, 159. Dublin, I. I and Marks, H, H 3951 601h An. Mits Assoc. Life Insurance Mted. Dır. of America Q7n3 Ini Ingle, L. 1933 Science, 78, 313. snadnout. A 1. V tary 1 - 7., 76, 235. : mil. Colloy. Acaine. Court's Problem of Apeine. Nou., Ch. vi, Baltimore: I JUU 1.NL 102 19.). Nutr. 3, 23). 0, II. S. 1941. J. Nutr., ·Nutrition and Ageing 109 1013 -- Runabom, 2,469. Amer. . 11) Sius, 175, 114, Robinson, D. S. and Poole, !.C F. 1956 Quart. J. exp. Physiol , 41, 36, Rinta 1067 A ! J. Anar , 81, 445. 1949. j. Nutr., 37, 317. SILSIT, H. M 1978. Vitam and Hormt, 6, 101, Saclair, HM 1951. New Engl J Med. 245, 39. Sinclar, HM 1952 Symp biochem Soc, 9, 80 Sociair, H M. 1955a Ciba Found Collog Ageing, 1, 194. Sinclair, H. M. 1955b. In Old Age in the Modern World, p 160, Edinburgh: Livingstone Sinclair, 1 M 19562 Lancet, i, 381. Sinclair, H M 1956. Lancel, ui, 101, Sinclair, 11. M 1956c Proc Nutr Soc., 15. xvui Sinclair, H. M 1956d Proc. 3rd Internal Congr. Lapids, Brussels, Smith, C.A 1947 Amer. J. Obstet Gynec, 53, 599. Stewbete. G., Slaton, W H UR , Howton, D R. and Mead, J F. 1956 J. brol Chem, 220, 257. Tannenbaum, A 1917 An NY Acad Sci., 49, 6 Templeto, It A and Ershaft, A. 1949. Amer. J. Physiol, 159, 33. Wilson, D C and Sutherland, I 1953. Brut med J, , 607 Wieren, P. W. and Holman, R. T. 1952. Arch Biochem, 41, 266. DISCUSSION GPL files. I do not presume to argue with De Carlin - ohn 4. Pisey. Among the chemical Arromas ageing, there at ·108 Sinclair ...711-". I. eating, and this increase is undesirable. There is a conflict of opinion about calcium requirements of the elderly: osteoporosis is probably more related to failure of protein anabolism than to dietary calcium deficiency. The most important effects of senescence upon nutrition are those associated with conditions that are all too often found in old persons: poverty, ignorance and apathy. References Armstrong, D. B, Dublin, L. I, Wheatley, G. 41, and Marks, 11. 11, 1951. J. Amer. med. Ass., 147, 1007. Basnayake, V and Sinclair, H. M. 1954. J. Phisiol, 126, SSP. Basnayake, V and Sinclair, H. M. 1955. Proc. 2nd Internat. Congr. Lipids, Ghent Bishopp, F. C. and Smith, C, N, 1938. U.S. Dept Agric., Circ., 478. Bonham Carter, R E., Dent, CE, Fowler, D. and Harper, C. M. 1955 Arck Dis. Childh , 153, 399. Na York. Reinhold. . ... 363 ! 176 248 Amer Ohstet Gyner, 56,904 Cornaro, L. 1558. Trattato della wta sobria Padova. Perchacino. Dublin, LI 1930. Hunt Biol., 2. 159 Dublin, L. and Maris, H. 1951 6011 An. Mig, Assoc. Life Insurance Med Dir of America Fischer-Preite, E. 1939 J. Conrh, 83, 303. Fritsch, R ). 1993 Z. KISS Zool, 157, 35 2557 Iers hohlbarheid Kovenhavn. T . 1, 76, 235. 1, 103. : - und. Collong Afrine, 1, 186. McCay, C. M. 1952. Cowdry's Problems of Agripp, 3rd e., Ch vi, Baltmore: Williams and Wilkins McCay, C. M, Dudley, W. Land Crowell, M. F. 1929, Nutr. 1, McCay, C. M., Maynard, L. A., Sperling, G. and Osgood, IS 1941 . Nutr. 21, 43.

·DIORAH SHOWTO A PROPOSED MECHANISM FOR THE FORMATIOY OF AN ANTI-LIPACMIC FACTOR Slastin; C. Collagen; OS, Ground Substance; S.P. Sulphated Polysaocharides; C.F., Clearing Factor, LP, Lipoprotein; Sol, Soluble; -se, Negatne. -VE.-Neutral L.P. FA™s ACID FATS AND CHOLESTROL EM: Lipo-Microns dissolved SSEL Sol. Stable SP.- Orthochromatic Elastase E.M.: Elasto-mucin Inhibitor globulin) Soluble Elastase Unstable SP.: Metachromatic Nutrition and Ageing -VE, ATHEROMA production Degraded products ASMA C.F. of HYPER LIPAEMIC PLASMA lipo-microns and chylomicrons Chondroitin Elastase+SP. Sulphate and Heparin serum Inhibitor 111 ·110 Discussion enough is already known to indicate that, even if they do not start the degenerative atherosclerotic process, they contribute to its progress. Over the last forty years, many attempts have been made to incriminate one or more single fatty constituents of the serum. Thus, it has been supposed that a high level of blood cholesterol can lead to atherom.; certainly feeding experiments in rabbits suggest that this is the case. Others bave incriminated the lipids in general, and so on. My own observations strongly suggest that deposition of the fatty materials in the walls of arteries is facilitated, or perhaps even directly caused, by disproportion of the main fatty substances in the blood. Normally, the ratio between cholesterol and phospholipids is 1:1, but, in association with active atherosclerosis, this lipolytic quotient is usually miral hunt mat he layanad Cnmachintha muntant Amenhen polytic quotieat to revert to normal, and by reducing the abnormally high beta fraction of the lipo-proteins. It seems to follow that rescarch ---- lecithin-fraction from soya beans, together with other surfacc-active agents, but already it is possible to assert that, in most cases, the pathologically altered lipid-spectrum reverts to normal or nearly normal. Miss H. Saxl. Recent research carried out at the University of Leeds by the Nuffield Gerontological Research Unit indicates that an antilipaemic factor is formed in tissues which are rich in mucopolysaccharides such as the connective tissues of the vascular system, the liver and the blood, by the interaction of the pancreatic enzyme clastasc with certain components of the serum. The following mechanism has been suggested for the reaction and is shown on the diagram. A. In the presence of elastase and especially the fraction which has clastomucasc activity, the mucopolysaccharides are made soluble and unstable. B. The serum inhibitor for the enzyme clastase is related to the x-globulin fraction. Its action is to control the enzyme in the formation of degradation products. This was estimated as a proteolytic function with biochemical methods and it also inhibits the removal of the soluble polysaccharides and makes them stable. Histological studies indicate that metachromatic substances become orthochromatic and that an absorption complex of the orthochromatic and elastica staining substances occurs which has the appearance of an amorphous clastin under the clectron microscope. nin ·DIAGRAM SHOWING A PROPOSED MICHANISM FOR THE FORMATION OF AN ANTI-LIPAEMIC FACTOR Ejastın; C. Collagen; OS, Ground Substances SP Sulphated Polysaccharides; CF, Clearing Factor; LP., Lipoprotein; Sol.. Soluble; -ve, Negative. --VE. Neutral L.P. Fat's ACID FATS AND CHOLESTROL E.M.: Lipo-Microns dissolved SSEL Sol. Stable S.P.- Orthochromatic Elastase E.M.: Elasto-mucin Inhibitor (globulin) Soluble Elastase Unstable SP.: Mecachromatic Nutrition and Ageing -VE, ATHEROMA production Degraded products LASMA C.F. of HYPER LIPAEMIC PLASMA lipo.microns and chylomicrons 111 Chondroitin Elastase+S.P. Sulphate and Heparin +-serum inhibitor ·110 Discussion enough is already known to indicate that, even if they do not start the degenerative atherosclerotic process, they contribute to its progress. Over the last forty years, many attempts have been made to incriminate one or more single fatty constituents of the serum. Thus, it has been supposed that a high level of blood cholesterol can lead to atheroma; certainly feeding experiments in rabbits suggest that this is the case. Others have incriminated the lipids in general, and so on. My own observations strongly suggest that deposition of the fatty materials in the walls of arteries is facilitated, or perhaps even directly caused by disproportios of the main fatty substances in the blood. Normally, the ratio between cholesterol and phospholipids ss 1:1, but, ia association with active atherosclerosis, this lipolytic quotient is usually raised but may be lowered. Some shift of the quotient seems to be a part of the ageing process, so that the idea that atheroma itself is an ineluciabic consequence of innumerable microtraumata throughout life is not wholly acceptable. Furthermore, there is now a good deal of evidence that the rate of deposition in the arterial walls can be slowed by causing the lipolytic quotient to revert to normal, and by reducing the abnormally Miss H. Saxl. Recent research carried out at the University of Leeds by the Nuffield Gerontological Research Unit indicates that an antilipacmc factor is formed in tissues which are rich in mucopolysaccharides such as the connective tissues of the vascular system, the lives and the in a plachen with certain 1 A. In the preseace of ciastase and especially the traction woch mas clastomucasc activity, the mucopolysaccharides are made soluble and vastable. 3 The serum inhibitor for the enzymc ciastase is related to the the main the formation stances occurs which has the appearance of an amorphous clastin under the electron microscope. C. As a result of the above interaction, a sipase is activated. Dio. chemical investigations indicate that the quantity of inhibition is directly *n the amount of linnlvris. The lipase destades neuira! on the lipids of vascular tissue factor",

·Nutrition and Ageing
113
H. M. Sinclair, The effect of the introduction of electrocardiograms
was allowed for in the study on coronary thrombosis

·112 Discussion The classical discovery of Anitschkow, who produced a lesion simulating human atherosclerosis by feeding rabbits with cholesterol, has resulted in an intensivc effort over the last twenty years to link atherosclerosis to a faulty lipid metabolism. Anítschkow observed that if the ingestion of cholesterol was discontinued after the feeding had been carried out for 3-4 months, a resorption of lipid occurred in the inner layers of the arterial wall, although the characteristic lipid plaquc remained in the media for a much longer time. Studies of the localization of the enzyme action point to the fact that the high concentration of polysaccharides in the inner layers of the vascular wall, together with an elastomucasc, protects these against the deposition of the lipid. This would explain the observations of Anitschkow that the lipid was absorbed from the intima of the arterial wall after the cessation of the cholesterol feeding G. C. Kennedy. I wonder if it is too inconoclastic to question the significance that has been attached to these "classic" papers of McCay's that Dr. Sinclair and several other speakers have mentioned. It is truc, is it not, that McCay had to make scvcral attempts before he could get the T. did not seem to be a cause of death, and the incidence was unaffected by T brcakdown occurs quite rapidly even in young rats, and is accompanied by loss of weight, staring fur and a general appearance such as is shown in McCay's pictures of "old" rats. I think it is simply the appearance of the chronic uracmic rat. E. Disby. I doubt whether the cffects of under and over-nourishment are always as stated. There is much under-nourishment in India and China but the general impression is that both maturation and pubcrty orc carlier there than in Western Europe. G. H. Bourne. The answer to Mir. Digby is that maturity does not occur carlier in Eastern countrics. G. 1. M. Swyer. There is no evidence that Indian women are nubile at an carlier agc than Europeans. F. Le Gros Clark. I know of no real racial differences in the mutluration of human beings. There is some cyidence that in Belgium, wartime undernourishment led to a delay in the onset of puberty,

·GENETIC VARIATIONS IN AGEING
Ву
J. MAYNARD SMITH
Depariment of Zoology, University College, London, W.C. /
THERE are two kinds of differences between individuals which can
afnan awal
una
L.
is strictly relevant to the problem of ageing, because in neither case
does the susceptibility of an individual to the factor causing death
increase with age.
The study of ageing is concerned with those changes in individuals
with age which render them more liable to succumb to one or more
Li
J.AL
TL-.-.-
hoan v snow
T-.l.
- 3
genetically homogeneous population of the fruitdy, Drosophila
subobscura, kept in mated pairs at 25°C, and transferred to fresh
food every second day. In no case is it possible to state the cause
nf daoth !
....1
:...MU. Apustu lu Nera.
Figure 1 also shows that life span is, in this and most other
populations, a continuously varying character. Individuals do not
fall into two or a few sharply defined classes. Sucb characters

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·Genetic Variations in Ageing 117 ever the danger in this procedure that maternal age itself may influence the longevity of the offspring In partheaogenetically reproducing rotifers, Lansing (1948) showed that lines maintained from the eggs laid by young mothers could be kept indefinitely, whereas if the later eggs laid by a female were used, there was a procressive decline in mean life span in successive generations, and -L-Arant sm11 For these reasons, there is less intormation VIL UIL BUL of ageing than of many other quantitative characters. However, what information there is is of some interest. I shall deserbe first some experiments on laboratory populations of Drosophila, and then consider how far these agree with observations on human populations, AP parents, which suggests that crossing unrelated animais inay give ------ OnThen be deleterious. By analogy, large random changes in a motor car engine would be more likely to reduce than to increase its efficiency. It is possible that a single mutation which lowered the metabolic rate, c-h ah data: 3 the lif cally ·116 Maynard Smith present special difficulties for genetical analysis for two reasons. First, the continuous distribution suggests that they are influenced by senes at many different loci, and second, they may be influenced by the environment as well as by genetic make-up. For example, the flies whose survival curve is shown in Figure I were kept as larvac and pupae at 25°C. Flics which were kept during pre-adult life at 15°C. survived for about 20 per cent longer as adults at 25°C. 25 20 15 NUMBER ALIVE S 4 8 12 16 20 28 32 36 40 44 49 AGE IN DAYS Fo 1.-Adult survival curves at 25°C. for the Fj hybrids between two inbred lines, B and K, of Drosophila subobscura. l'ull Itne, females, broken line, males The techniques available to a geneticist in the study of continuously varying characters include in wild populations measurements of the correlation betwcen sibs or between parents and offspring, and, in laboratory animals, investigation of the effects of changes in the breeding system, for example by inbreeding or distant hybridization, and of selection. Adult life span is in many ways an inconvcnient character for such studies, since it is not known until thic individual is dead. Thus sclection for a shortcr adult life span could be carried out only by brecding from a large number of pairs sct up at random, kccping the parents until they dicd of old age, and the survivors used as parents of the nexi gcncration. There is how- ·Genetic Variations in Ageing 117 ever the danger in this procedure that maternal age itself may influence the longevity of the offspring. In parthenogenetically reproducing rotiſers, Lansing (1948) showed that lines maintained from the eggs laid by young mothers could be kept indefinitely, whereas if the later eggs laid by a female were used, there was a progressive decline in mean life span in successive generations, and It is not known how general such an effect wilt organisms, but some special oid idiots have a low erpectathe children of old mothers For these reasons, there is less normation on the genetics of ---nge nther nuantitative characters. However, what Ivy or the If that ybrids, d-type VYTVE ...RU that there also exist recessive mutants for which homozygotes live of genes at a large number of loci. Aiman mantel -...

·116 Maynard Smith present specint First, the continus wuenced by genes at mat www, they may be influenced by the environt w well as by genetic make-up. For example, the flies whose survival curve is shown in Figure I were kept as larvac and pupae at 25°C. Flies which were kept during pre-adult life at 15°C. survived for about 20 per cent longer as adults at 25°C. 25 20 NUMBER ALIVE 5 4 8 12 16 20 24 20 32 36 44 48 ACE IN DAYS no. 1.. Adul sur ival cunes at :5°C for the Fi hybrids bctuen tho inbred lines, and K, of Drosophila subobscura. Pull line, females, broken line, males The techniques availablc to a gerclicist in the study of continu. ously varying characters include in wild populorions mcasurements of the correlation betweca sibs or between parents and oftspring, and, in laboratory animals, investigation of the effects of changes in the breeding system, for example by inbreeding or distant hybridization, and of selection. Adult life span is in many ways an inconvenient character for such studies, since it is not known until the individual is dead Thus selection for a shorter adult life span could be carricd out only by breeding from a large number of pairs sc! up at random, &ccping the parents until they died of old age, and continuing breeding from the oilspring of those parents" young. Selection for increased fitness can be kept firmata the survivors $ ·Generic Variations in Ageing 119 single locus, such that individuals with the genotype Aa lived -- fanphart time. First, selection would 18-lived heterozygotes, Aa x uch were short-lived homo- -Jou.., together two short-lived flies might pive nothing but short-lived offspring (if the mating were . Anninn lof the homozygous for different alleles al many u LULU,, ... hybridization restores both genetic heterozygosity and long life. The -- th no colantion would he ineffective and that inbreeding pairs ion of leterosis", in contrast to genes with additive" ettects, in wuuch the ALL rator closely associated with fitness, should show heterosis, whereas bristle number should show in the main additive inheritance. Haldane (1949) showed that in a random mating population in cquilibrium under the influence of natural selection, no correlation would be expected between the fitness of parents and offspring, -1.1--LL... --'11 L. selection, being maintained at a low frequency only, by mutation. Therefore most of the genetic variance of fitness will be heterotic. It has already been pointed out that in this case there will be no ·wo 118 Maynard Smith cffects found by Lansing in rotifers operate also in Drosophila. The absence of any response to selection might suggest that the differences in longevity were environmental and not genetic in origin, This however is not the case. Figure 2 shows survival curves for 100 90 D/K 80 70 60 Numer art SO 40 30 20 10 0 10 20 30 49 50 80 70 80 90 100 Age in dys FIG. 2.-Aduit survival cumcs (sexes combined) at 19° C for two inbred lines, Band K, of Drosophila subobscura, and of the r, hybrids belucen them (Clarke & Maynard Smith, 1935), two inbred lines of O, subobscura, and for the reciprocal hybrids between them, kept as far as possible in identical conditions The mcan expectation of life of the hybrids is approximately twice that of the inbred fics, and the difference is largcly or wholly genetic. It will be recalled that Pcari afso found that F, hybreds lived longer than their parents, but the difference in the present case was far greater, probably because the parental flies were highly inbred It should not be thought that these results demonstrate that hybridization increases the life span above that normal for the species. The offspring of fertilized females caught in the wild lived in laboratory conditions for as long as did these hybrids, although there was a small proportion of very short-lived flies among the offspring of wild females. Thus the explanation of these results is that inbreeding greatly reduced the normal life span, which was restored by crossing the inbred lines, The simplest explanation of these facts is that genetic heterozygoles live for longer than do homozygotes. Consider what would happen if differences in longevity were due to a pair of alleles, and a, at a ·Genetic Variations in Ageing 119 single locis, such that individuals with the genotype Ad lived uld х nozygotes, AA or aa, whereas mating together two short-lived Nies might give notblog but short-lived offspring (if the mating were ARX A4 APNA V nol or nothian hinn 1: .d ... mating between inbred lines tend to become many of these loci, so that huhridization recorre hath want load Heterozyente 19 intermediate hate an- it genes w . I. riance of the gumber • has been shown by . rs to be due in the Paw! W genes with additive effects, or showing sitnim dominonen ... miss, SUOUIQ show heterosis, whereas bristič number should show in the main additive inheritance. Haldane (1949) showed that is a random maling population in equilibrium under the influence of natural selection, no correlation would be expected between the fitness of parents and offspring, although there will be a substantial carrains - 1. susu ilu lesponse to selection. To put Loc matter is another way, if natural selection has alsondu -... mized ftness, it is imner?'

·120 Maynard Smith selection. The same will be true of characters such as longevity which are closely associated with fitness, although it might be possible to increase the mean life span by selection at the expense of reduced fitness in other ways, for example reduced fertility. There is some evidence that the genetic variance of longevity in man is in the main due to genes with heterotic effects. Beeton and Pearson (1901) measured parent-offspring and sib-sib correlations for man fannot nsure that the same ecor obtained were caused by genetic rather than environmental factors. They considered only those children who died at 21 or later, on the grounds that the causes of death in infancy and in later life are different. The mean value of the four parent-offspring correlations was 0.1365, or only about one-quarter of that for human stature, and of the three sib-sib correlations 0.2611. The higher value of the latter correlation is what would be expected from Haldane's argu- TLthe of ageing is most easily studied in mammals, since too little is known of the pathology of most other groups to determine the cause of death. There is little doubt that animals of similar genotypes, kept in conditions in which there are few accidental deaths, tend to die of similar causes. For example, inbred lines of mice differ not only in the age of onset of cancers, but also in the particular kinds of cancer which develop. Similarly, different breeds of domestic dogs INFO er al (1954) measured the arterial pressure in the relatives of patients with "normal" blood pressures, and of patients with essential hypertension i.e. in patients with blood pressures higher than an arbitrarily selected value, and having no disease to which these pressures could be attributed. When allowance was made for differences due to age and sex, the blood pressures of the former group of relatives did not differ from the general population, whercas the pressures of relatives of patients with essential hypertension were higher, the excess for the relatives over the normal for their age and sex being about 20 per cent of that for the affected patients. aination of the blood obably in fluenced also by environmental factors. These results have been quoted for two reasons. First, they con. firm that genetic factors influence a particular process which may

·Genetic Variations in Ageing
121
tahide to death in old age. Second, it was found that the
-antne that
>
1
it
may exist between expecialioul Uluu uuu una
-Itha shility to withstand one particular group of
1
perhaps earner i ule, Ilutului UACUUM
1...... antimal value If so, we
--
References
Beeton, M and Pearson K 1901 "On the inheritance of the duration of life,
and on the intensity of natural selection in man." Biometrika, 1, 50-89.
Bridges, E L. 1948 Ultermost part of the Earth. London Hodder &
Stoughton
Clarke, J. M and Maynard Smith, J 1955. “The genetics and cytology of
Drosophila subobscura XI. Hybrid vigour and longevity." J Genet , 53,
172-180
Comfort, A 1953 "Absence of a Lansing effect ia Drosophila subobscura"
Nature, Lont, 172, 83,

·120 Maynard Smith selection. The same wi}} be true of characters such as longevity which are closely associated with fitness, although it might be possible to increase the mean life span by selection at the expense of reduced fitness in other ways, for example reduced fertility. There longevity in man is ir Beeton and Pearson correlations for hum: ensure that the measured individuals were as far as possible living in the same economic conditions, and therefore that any correlations obtained were caused by genetic rather than environmental factors. They considered only those children who died at 21 or later, on the grounds that the causes of death in infancy and in later hfe are different. The mean value of the four parent-offspring correlations was 0.1365, or only about one-quarter of that for human stature, and of the three sib-sıb correlations 0.2611. Thic higher value of the latter correlation is what would be expected from Haldane's argu- *** ne you must -- its life span but also the particular cause us utalii. IHS usput us the genetics of ageing is most easily studied in mammals, since too little is known of the pathology of most other groups to determune the cause of death. There is little doubt that animals of similar genotypes, kept in conditions in which •. a anaitanont panthe tand in him of similar causes For .. in the age of onset of . cancer which develop. Similarly, different breds of domestic dogs ter ***ia. Tininhin 1054) . JA er á (1954) measured the arterial pressure in the relatives of patients with "normal" blood pressures, and of patients with "essential hypertension", i.e. in patients with blood pressurcs higher than an arbitrarily selected valus, and having no discase to which these pressures could be attributed. When allowance was made for differences due to age and sex, the blood pressures of the former group of relatives did not differ from the general population, whercas the pressures of relatives of patients with essential hypertension were higher, the excess for the relatives over the normal for their .ments nationte First, they con- "'ocess which may ·AUTHOR INDEX ·122 Maynard Smith Cotchin, E. 1954. “Neoplasia in the dog" Ver. Rec., 66, 879-885. Haldane, J.B S. 1949. “Parental and fraternal correlations for fitness." Anr Eugen., Lond, 14, 288-292. Hamilton, M., Pickering, G. W., Fraser Roberts, J. A. and Sowry, G. S. C 1954. " The aetiology of essential hypertension. IV. The role of inheritance." Clin. Sci., 13, 273-304. Hollingsworth, M. J. and Maynard Smith, J. 1953. "The effects of inbreeding on rate of development and on fertility in Drosopinla subobscura." J Genci. 53, 295-314, Lansing, A. I. 1948 "Evidence for ageing as a consequence of growth cessation." Proc nar. Acad Sci. IVash, 34, 301-310 Mather, K. and Harrison, B J. 1949. "The manifold effect of sclection." Heredity, 3, 1-52 and 131-162. Pearl, R. 1928. The Rate of Living. University of London Press Penrose, L. S 1954 * Mongolian Idiocy (mongolism) and maternal age." Ann. N Y. Acad. Sci., 57, 494. N. IV Pirie War ol.. DISCUSSION E Cwwl Lo the community Ivwul in some other way abnormal? Maynard Smith. The group chosen was not a random sample: it was drawn from Quaker families. The community was unlikely to have been abnormal since in the same population quite high correlation was found for other characters such as statute.

·AUTHOR INDEX The following index refers to the pages on which contributions by persons named are to be found it does not include the names of persons whose papers have been cited as references Barlow, H W B, 22 Levitt, T, 79, 113 Benjamun, B, XIV, 55, 68, 69, 86 Ludford, R.J. 45 Bourdiere, F, 211, 27 Bourne, G, H, I, 35, 44, 45, 112 Mayne, W. W , 89 Bradford, MS E.A. M, 72 Miles, GPL, 109 Case, R. AM, 68, 70 Clark, F le Gros, ix, 81, 112 Piney, A., 109 Cloudsley-Thompson, JL, 26, 33 Pire, N. W, 1x, 44, 68,122 Comfort, A., X, XII, XY, 23, 26 Saxl, H, 110 Digby, E, 45, 69, 112 Sinclair, H. M , xi, 101, 113 Droop, M R,7 Smith, J. Maynard, Xul, 115, 122 Swyer, G L M , xin, 47, 112 Gregory, F. G. 21 Hamuton, J B, 33, 53 Townsend, P., 68 Heath, O V S, X1, 7, 9, 21 Hero, A , XIV, 91 Verzar, F., 100 Hinshelwood, Sur Cynl, x, 1,7 Hobson, w, xv, 73, 79 Wangermann, E, 20 Kennedy, G C, 44,112 Worrall, R. L., 26, 33 Kershaw, WE, 89 Kock, PC De, 22 Yapp, W B, Y, 26

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·SUBJECT INDEX Bats, 31 Accidenis, proneness to, 76 Essential fatty acids, los Adrenal glands, 10 Evolutionary interpretation of scnc Ageug. defution of, it scence, 25 Ansvans, 32 Expenence of aged, utilization of, 100 Animals, 23-25 Arthnas, 24 Fertility, changes in. 56 Atheroia, 107 Fishes, 30 Atherosclerosis, 109 Fitness for surtival, 239 Flowering in plaats, 17 Bacteria, X1, 1-7 Food and ageing. 23, 101 , restriction, 28 Blood cells, 35 Buds, 24, 26 Genetic variations in ageing, 115-122 Blood pressure, 74, 120 Golgi apparatus, 37 Bronchus, 77 Gonads, 47 Bosterflies, 29, 101 Grayling. 30 Growth to plants, 12 Calcium deposition, 73 oves-rapid, 103 Carndrum, 10 Curca gigs, 24 Cardiovascular disease, 77 Cartilage, 42 Haemophilia, 115 Catalysas, tsbau of, 36 Slears, 93 Cattle, 89, 102 Hlomoiothermuc animals, 27 Cell membranes, 107 Hormones, X, 42 Cells, agerak of, XXL, 35-46 Harses, 82 malignant, 45 Housing of elderly, 6) Changes in bodily functions with age, 73-80 Inbreeding and reduction of life styan, Cholesterol, 130,212 118 Chronuc sickness, 71 Inheritance, 233, 120 Climactere un males, 49 Intelligence and ageing, 76 Cohort analysis, 76 Iron, excess of an old rurs, 38 Coronary thrombosis, 106 Caltor plant, 13 Creative work, 92 Kidney, cells of, 35 Cryplozoic animals, 33 Leanulag in relation to age, 95 Leaves of plants, 11 Daphnia, 28, 101, 101 Life span, of Drosophila, 136, 117 Dealness, 73 Limpets, 101 Demographic aspects of ageing. 55-72 Liver, ageing of, 44 Deoxyribose Trucleic acid, 2.35 cells of, 35 Lizards, 31 Dependancy of the elderly, 59, 68, 72 Deterioration of body, 100 Logarithme growth, 2 Plet, X1, 34 Lymezina dispar, 29, 101 Dogs, 21, 120 Drosophila, 28, 29, 101, 102, 104, IIS Measles, 115 Memory defects, 96 Elephants, 83 Menopause, 48 Employment of the elderly, 61, 62,75 Metabolic rate, xu Endocrinc glands, 42 Metabolism, 27-34 Endrocrinology and ageing. 47-54 More, 102, 120 Enzymes, 3, 40.41 Milk, consumption of, and ageing, Erythrocytes, 35, 38 JDS, 109 Mitochondria, 36 Death rate, 68, 70

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·SUBJECT INDEX Accidents, proneness to, 76 Essential fatty acids, 105 Adrenal glands, 50 Evolutionary interpretation of sene- Ageing, definition of, ex scence, 2$ Amphibians, 31 Experience of aged, utilization of, 100 Antals, 23-25 Arthritis, 74 Fertility, changes in, 56 Atheroma, 107 Fishes, 30 Atherosclerosis, 109 Fitness for survival, 119 Flowering in plants, 17 Bacteria, xi, 1-7 Food and ageing. 23, 101 Bats, 31 restriction, 28 Blood cells, 35 Birds, 24, 26 Genetic variations in ageing, 115-122 Blood pressure, 74, 120 Golgi apparatus, 37 Bronchitis, 77 Gonads, 47 Butterflics, 29, 101 Grayling, 30 Growth in plants. 12 Calcium deposition, 73 over-rapid, 103 Cambium, 10 Guinea pigs, 24 Cardiovascular disease, 77 Carolage, 42 Haemophilia, 115 Catalysts, exhaustion of, 36 Heang, 93 Cattle, 89, 102 Homoiother animals, 27 Cell membranes, 107 Hommodes, 11, 42 Cells, ageing of, xu, 35-46 Horses, 82 malignant, 45 Housing of elderly, 63 Changes in bodily functions with age, 73-80 Inbreeding and reduction of life span, Cholesterol, 110, 112 118 Chronc sickness, 77 Inheritance, xiu, 120 Climacteric in males, 49 Intelligence and ageing, 76 Cohort analysis, 70 Iron, excess of ra old rats, 38 Coronary thrombosis, 106 Coiton plant, 13 Kidney, cells of, 35 Creative work, 92 Cryptozoic anuals, 33 Learning in relation to age, 95 Leaves of plants, 11 Daphnio, 28, 101, 104 Deafness, 75 Life span, of Drosophila, 116, 117 Death rate, 68, 70 Lumpets, tot Liver, ageing of, 44 Demographic aspects of ageing, 53-72 Deotynbosc nucleic acid, 1,35 cells of, 35 Derendancy of the elderly, 59, 68, 72 Lizards, 31 Deitrioration of body, 100 Logarithnic growth, 2 Diet, x3), 74 Lymantra dispar, 29, 101 Dogs, 24, 120 Drosophila, 28, 29, 101, 102, 104, U15 Measles, 115 Memory defects, 96 Elephants, 83 Menopause, 48 Employment of the elderly, 61, 62,75 Metabolic rats, u Endocrine glands, 42 Metabolism, 27-34 Endocrinology and Egsang, 47-54 Mice, 102, 120 Enzymes, 3, 40.4) Mük, consumption of, and ageing, Erythrocytes, 35, 38 106, 109 Mitochondna, 36 ·128 Subject Index Nitosis, 35, 45 Salivary glands, cells of, 35, 36 Moina macrocona, 28 Sel anemones, 23 A tortality, changes in, 56 Selection, artificial, 121 Muscle, cells of sirialed, 35 eflect on hfe span, 117 Sequoia, xi, 10 Nematodes, 23 Sexual activity and senesocnce, xi 47 Nutrition and ageing, 101-13 Sickness, increase of, with age, 61 Sila norms, 101 Obesity and ageing, 104 Sysal, 19 Oestrogens, 50 Skin, cells of, 35 Oogenesis, 48 Spermatogenesis, 48 Steroids, S1-53 Pantothenic acid, 104 Steroidogenesis, si Parasites, longevity of, 89 Sticklebacks, 30 Porella vulgata, 30 Perception, 92 Tadpoles, 10L Periodic growth in bacterial cultures, 6 Temperature and ageing, 23 Permeability of cells, 37 Tamnam - Phosphatascs, 39 Plants, 9-12 Pigment, accumulation with age, 39 Pichards, 30 Trees, 9 Poiksiotherinic animals, 27 Tribolem confuss, 101 Population of England and Wales, 57 Trout, 102 Populations, ageing of, ss Tumours, 112, 113 Protozou, IO2 Psychological changes with age, 91- 100 Undernourishnsent and prolongation Puberty, affected by nourishment, 103 of life, sol, 102 Rats, 102, 104 Vertigo, 75 Rejuvenation, 47 Visual acuity, 75 Renal diseases, 112 Vision, 77,93 Reproduction in plants, 10 Repuiles, 31 Working ability, 97 Respiratory infections, 112 Working life, 61 Retirement, age of, 68, 78, 84 as a measure of ageing, 81-90 Rotifers, 23, 29, 38, 104, 117, 118 -, of animals, xiv, 82-84

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