Skip to main content
SpringerLink
Log in

Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress

  • Review Articles
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

Cytogerontology, the science of cellular ageing, originated in 1881 with the prediction by August Weismann that the somatic cells of higher animals have limited division potential. Weismann's prediction was derived by considering the role of natural selection in regulating the duration of an organism's life. For various reasons, Weismann's ideas on ageing fell into neglect following his death in 1914, and cytogerontology has only reappeared as a major research area following the demonstration by Hayflick and Moorhead in the early 1960s that diploid human fibroblasts are restricted to a finite number of divisions in vitro.

In this review we give a detailed account of Weismann's theory, and we reveal that his ideas were both more extensive in their scope and more pertinent to current research than is generally recognised. We also appraise the progress which has been made over the past hundred years in investigating the causes of ageing, with particular emphasis being given to (i) the evolution of ageing, and (ii) ageing at the cellular level. We critically assess the current state of knowledge in these areas and recommend a series of points as primary targets for future research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bell E, Marek LF, Levinstone DS, Merrill C, Sher S, Young IT, Eden M (1978) Loss of division potentialin vitro: aging or differentiation? Science 202:1158–1163

    Google Scholar 

  • Bidder GP (1932) Senescence. Br Med J ii:583–585

    Google Scholar 

  • Bjorksten J (1968) The crosslinkage theory of ageing. J Am Geriatr Soc 16:408–427

    Google Scholar 

  • Brash DE, Hart RW (1978) Molecular biology of aging. In: Behnke JA, Finch CE, Moment GB (eds) The biology of ageing. Plenum Press, New York, pp 57–81

    Google Scholar 

  • Bunn CL, Tarrant GM (1980) Limited lifespan in somatic cell hybrids. Exp Cell Res 127:385–396

    Google Scholar 

  • Burnet FM (1974) Intrinsic mutagenesis: a genetic approach to ageing. Wiley, New York

    Google Scholar 

  • Calow P (1978) Bidder's hypothesis revisited: solution to some key problems associated with general molecular theory of ageing. Gerontology 24:448–458

    Google Scholar 

  • Carrel A (1912) On the permanent life of tissues outside of the organism. J Exp Med 15:516–527

    Google Scholar 

  • Charlesworth B (1980) Evolution in age-structured populations. Cambridge University Press, Cambridge

    Google Scholar 

  • Child CM (1911) A study of senescence and rejuvenescence based on experiments withPlanaria dorotocephata. Arch Entw Mech Org 31: 537–616

    Google Scholar 

  • Child CM (1915) Senescence and rejuvenescence. University of Chicago Press, Chicago

    Google Scholar 

  • Cole LC (1954) The population consequences of life history phenomena. Q Rev Biol 29:103–137

    Google Scholar 

  • Comfort A (1979) The biology of senescence, 3rd edn. Churchill Livingstone, Edinburgh

    Google Scholar 

  • Cremer T, Werdan K, Stevenson AFG, Lehner K, Messerschmidt O (1981) Agingin vitro and D-glucose uptake kinetics of diploid human fibroblasts. J Cell Physiol 106:99–108

    Google Scholar 

  • Curtis HJ (1966) Biological mechanisms of aging. Charles C Thomas, Springfield, Illinois

    Google Scholar 

  • Cutler RG (1975) Evolution of human longevity and the genetic complexity governing aging rate. Proc Natl Acad Sci USA 72: 4664–4668

    Google Scholar 

  • Cutler RG (1978) Evolutionary biology of senescence. In: Behnke JA, Finch CE, Moment GB (eds) The biology of aging. Plenum Press, New York

    Google Scholar 

  • Daniel CW (1973) Finite growth of mouse mammary gland serially propagatedin vivo. Experientia 29:1422–1424

    Google Scholar 

  • Darwin C (1872) The origin of species by means of natural selection, 6th edn, chap V “Compensation and economy of growth” J Murray, London

    Google Scholar 

  • De Long R, Poplin L (1977) On the etiology of aging. J Theor Biol 67: 111–120

    Google Scholar 

  • Ebeling AH (1913) The permanent life of connective tissue outside of the organism. J Exp Med 17:273–285

    Google Scholar 

  • Epstein CJ, Martin GM, Schultz AL, Motulsky AG (1966) Werner's syndrome: a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine 45:177–221

    Google Scholar 

  • Evans CH (1977) Further evidence against the accumulation of altered enzymes in late passage mouse fibroblastsin vitro. Exp Gerontol 12:169–171

    Google Scholar 

  • Fulder SJ, Holliday R (1975) A rapid rise in cell variants during the senescence of populations of human fibroblasts. Cell 6:67–73

    Google Scholar 

  • Götte A (1883) Über den Ursprung des Todes. L Voss, Hamburg Leipzig

    Google Scholar 

  • Guthrie RD (1969) Senescence as an adaptive trait. Persp Biol Med 12: 313–324

    Google Scholar 

  • Haldane JBS (1941) New paths in genetics. George Allen & Unwin, London

    Google Scholar 

  • Hamilton WD (1966) The moulding of senescence by natural selection. J Theor Biol 12:12–45

    Google Scholar 

  • Harley CB, Goldstein S (1978) Cultured human fibroblasts: distribution of cell generations and a critical limit. J Cell Physiol 97:509–516

    Google Scholar 

  • Harley CB, Pollard JW, Chamberlain JW, Stanners CP, Goldstein S (1980) Protein synthetic errors do not increase during aging of cultured human fibroblasts. Proc Natl Acad Sci USA 77:1885–1889

    Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    Google Scholar 

  • Hart RW, Setlow RB (1974) Correlation between deoxyribonucleic acid excision-repair and lifespan in a number of mammalian species. Proc Natl Acad Sci USA 71:2169–2173

    Google Scholar 

  • Hayflick L (1965) The limitedin vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636

    Google Scholar 

  • Hayflick L (1977) The cellular basis for human ageing. In: Finch CE, Hayflick L (eds) Handbook of the biology of aging. Van Nostrand-Reinhold, New York, pp 159–186

    Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Google Scholar 

  • Hill B, Franks LM (1977) The mechanism of ageing. Trends Biochem Sci 2:N80-N82

    Google Scholar 

  • Hirsch HR (1978) The waste-product theory of ageing: waste dilution by cell division. Mech Ageing Dev 8:51–62

    Google Scholar 

  • Holliday R (1974) Growth and death of diploid and transformed human fibroblasts. Fedn Proc 34:51–55

    Google Scholar 

  • Holliday R (1979) A new theory of carcinogenesis. Br J Cancer 40: 513–522

    Google Scholar 

  • Holliday R, Tarrant GM (1972) Altered enzymes in ageing human fibroblasts. Nature 238:26–30

    Google Scholar 

  • Holliday R, Kirkwood TBL (1981) Predictions of the somatic mutation and mortalisation theories of cellular ageing are contrary to experimental observations. J Theor Biol 93:627–642

    Google Scholar 

  • Holliday R, Porterfield JS, Gibbs DD (1974) Premature ageing and occurrence of altered enzyme in Werner's syndrome fibroblasts. Nature 248:762–763

    Google Scholar 

  • Holliday R, Huschtscha LI, Tarrant GM, Kirkwood TBL (1977) Testing the commitment theory of cellular aging. Science 198:366–372

    Google Scholar 

  • Holliday R, Huschtscha LI, Kirkwood TBL (1981) Cellular aging: further evidence for the commitment theory. Science 213:1505–1508

    Google Scholar 

  • Illmensee K, Stevens LC (1979) Teratomas and chimeras. Sci Am 240: 87–98

    Google Scholar 

  • Kay HEM (1965) How many cell generations? Lancet ii:418–419

    Google Scholar 

  • Kirkwood TBL (1977) Evolution of ageing. Nature 270:301–304

    Google Scholar 

  • Kirkwood TBL (1980) Error propagation in intracellular information transfer. J Theor Biol 82:363–382

    Google Scholar 

  • Kirkwood TBL (1981) Repair and its evolution: survival versus reproduction. In: Townsend CR, Calow P (eds) Physiological ecology: an evolutionary approach to resource use. Blackwell, Oxford, pp 165–189

    Google Scholar 

  • Kirkwood TBL, Holliday R (1975) Commitment to senescence: a model for the finite and infinite growth of diploid and transformed human fibroblasts in culture. J Theor Biol 53:481–496

    Google Scholar 

  • Kirkwood TBL, Holliday R (1979) The evolution of ageing and longevity. Proc R Soc Lond B 205:531–546

    Google Scholar 

  • Kontermann K, Bayreuther K (1979) The cellular aging of rat fibroblastsin vitro is a differentiation process. Gerontology 25:261–274

    Google Scholar 

  • Kram D, Schneider EL (1978) Parental age effects: increased frequencies of genetically abnormal offspring. In: Schneider EL (ed) The genetics of aging. Plenum Press, New York, pp 225–260

    Google Scholar 

  • Krohn PL (1962) Review lectures on senescence. II. Heterochronic transplantation in the study of ageing. Proc R Soc Lond B 157: 128–147

    Google Scholar 

  • Lack D (1954) The natural regulation of animal numbers. Clarendon Press, Oxford

    Google Scholar 

  • Linn S, Kairis M, Holliday R (1976) Decreased fidelity of DNA polymerase activity isolated from aging human fibroblasts. Proc Natl Acad Sci USA 73:2818–2822

    Google Scholar 

  • Martin GM (1977a) Cellular aging—clonal senescence. Am J Pathol 89:484–511

    Google Scholar 

  • Martin GM (1977b) Cellular aging—postreplicative cells. Am J Pathol 89:513–530

    Google Scholar 

  • Martin GM (1979) Genetic and evolutionary aspects of aging. Fed Proc 38:1962–1967

    Google Scholar 

  • Martin GM, Sprague CA, Epstein CJ (1970) Replicative lifespan of cultivated human cells: effect of donor's age, tissue and genotype. Lab Invest 23:86–92

    Google Scholar 

  • Martin GM, Sprague CA, Norwood TH, Pendergrass WR (1974) Clonal selection, attenuation and differentiation in anin vitro model of hyperplasia. Am J Pathol 74:137–154

    Google Scholar 

  • Martin GR (1980) Teratocarcinomas and mammalian embryogenesis. Science 209:768–776

    Google Scholar 

  • Martinez AO, Norwood TH, Prothero JW, Martin GM (1978) Evidence for clonal attenuation of growth potential in HeLa cells. In Vitro 14:996–1002

    Google Scholar 

  • Maynard Smith J (1962) Review lectures on senescence. I. The causes of ageing. Proc R Soc Lond B 157:115–127

    Google Scholar 

  • Maynard Smith J (1976) Group selection. Q Rev Biol 51:277–283

    Google Scholar 

  • Medawar PB (1946) Old age and natural death. Mod Quart 2 (new series):30–49

    Google Scholar 

  • Medawar PB (1952) An unsolved problem in biology. HK Lewis, London. (Reprinted in “The Uniqueness of the Individual”, Methuen, London 1957)

    Google Scholar 

  • Medvedev ZhA (1962) Ageing at the molecular level. In: Shock NW (ed) Biological aspects of ageing. Columbia University Press, New York, pp 255–266

    Google Scholar 

  • Medvedev ZhA (1981) On the immortality of the germ line: genetic and biochemical mechanisms—A review. Mech Ageing Dev 17:331–359

    Google Scholar 

  • Metchnikoff E (1907) The prolongation of life: optimistic studies. Heinemann, London

    Google Scholar 

  • Minot CS (1907) The problem of age, growth and death. Pop Sci Monthly 70:481–496; 71:97–120; 71:509–523

    Google Scholar 

  • Morley A, Cox S, Holliday R (1982) Human lymphocytes resistant to 6-thioguanine resistance increase with age. Mech Ageing Dev (in press)

  • Muggleton-Harris AL, Hayflick L (1976) Cellular ageing studied by the reconstruction of replicating cells from nuclei and cytoplasms isolated from normal human diploid cells. Exp Cell Res 103:321–330

    Google Scholar 

  • Nienhaus AJ, de Jong B, ten Kate LP (1971) Fibroblast culture in Werner's syndrome. Humangenetik 13:244–246

    Google Scholar 

  • Ogden DA, Micklem HS (1976) The fate of serially transplanted bone marrow cell populations from young and old donors. Transplantation 22:287–293

    Google Scholar 

  • Orgel LE (1963) The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc Natl Acad Sci USA 49:517–521

    Google Scholar 

  • Orgel LE (1973) Ageing of clones of mammalian cells. Nature 243: 441–445

    Google Scholar 

  • Pearl R (1928) The rate of living. University of London Press, London

    Google Scholar 

  • Ponten J, Westermark B (1980) Cell generation and aging of nontransformed glial cells from adult humans. Adv Cellular Neurobiol 1:209–227

    Google Scholar 

  • Rose MR, Charlesworth B (1980) A test of evolutionary theories of senescence. Nature 287:141–142

    Google Scholar 

  • Rosenberger R, Kirkwood TBL (1982) The stability of the translation apparatus. In: Galas DJ (ed) Accuracy in molecular biology. Marcel Dekker, New York (in press)

    Google Scholar 

  • Rothfels KH, Kupelwieser EB, Parker RC (1963) Effects of X-irradiated feeder layers on mitotic activity and development of aneuploidy in mouse embryo cellsin vitro. Can Cancer Conf 5:191–223

    Google Scholar 

  • Sacher GA (1978) Evolution of longevity and survival characteristics in mammals. In: Schneider EL (ed) The Genetics of aging. Plenum Press, New York, pp 151–167

    Google Scholar 

  • Schneider EL, Mitsui Y (1976) The relationship betweenin vitro cellular aging andin vivo human age. Proc Natl Acad Sci USA 73:3584–3588

    Google Scholar 

  • Sheldrake AR (1974) The ageing, growth and death of cells. Nature 250:381–385

    Google Scholar 

  • Smith JR, Hayflick L (1974) Variation in the life-span of clones derived from human diploid cell strains. J Cell Biol 62:48–53

    Google Scholar 

  • Smith JR, Whitney RG (1980) Intraclonal variation in proliferative potential of human diploid fibroblasts: stochastic mechanism for cellular aging. Science 207:82–84

    Google Scholar 

  • Smith JR, Pereira-Smith OM, Schneider EL (1978) Colony size distribution as a measure ofin vivo andin vitro aging. Proc Natl Acad Sci USA 75:1353–1356

    Google Scholar 

  • Smith-Sonneborn J (1979) DNA repair and longevity assurance inParamecium tetraurelia. Science 203:1115–1117

    Google Scholar 

  • Sonneborn TM (1930) Genetic studies onStenostomum incaudatum (nov spec). I. The nature and origin of differences among individuals formed during vegetative reproduction. J Exp Zool 57:57–108

    Google Scholar 

  • Sonneborn TM (1954) The relation of autogamy to senescence and rejuvenescence inParamecium aurelia. J Protozool 1:38–53

    Google Scholar 

  • Stanley JF, Pye D, MacGregor A (1975) Comparison of doubling numbers attained by cultured animal cells with lifespan of species. Nature 255:158–159

    Google Scholar 

  • Stecker E, Gardner HA (1970) Werner's syndrome. Lancet ii:1317

    Google Scholar 

  • Stein GH, Yanishevsky RM (1979) Entry into S phase is inhibited in two immortal cell lines fused to senescent human diploid cells. Exp Cell Res 120:155–165

    Google Scholar 

  • Stevens LC (1967) The biology of teratomas. In: Abercrombie M, Bracket J (eds) Advances in morphogenesis, vol 6. Academic Press, New York, pp 1–31

    Google Scholar 

  • Strehler BL (1977) Time, cells and aging, 2nd edn. Academic Press, New York

    Google Scholar 

  • Swim HE, Parker RF (1957) Culture characteristics of human fibroblasts propagated serially. Am J Hyg 66:235–243

    Google Scholar 

  • Szilard L (1959) On the nature of the aging process. Proc Natl Acad Sci USA 45:30–45

    Google Scholar 

  • Thompson KVA, Holliday R (1982) Genetic effects on thein vitro ageing of human fibroblasts. I. Werner's syndrome, Cockayne's syndrome and progeria. Gerontology (in preparation)

  • Todaro GJ, Green H (1963) Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol 17:299–313

    Google Scholar 

  • Topp W, Hall JD, Rifkin D, Levine AJ, Pollack R (1977) The characterisation of SV40-transformed cell lines derived from mouse teratocarcinoma: growth properties and differentiated characteristics. J Cell Physiol 93:269–276

    Google Scholar 

  • Vines SH (1889) An examination of some points in Prof. Weismann's theory of heredity. Nature 40:621–626

    Google Scholar 

  • Vogel F, Rathenberg R (1975) Spontaneous mutation in man. In: Harris H, Hirschhorn K (eds) Advances in human genetics, vol 5. Plenum Press, New York London, pp 223–318

    Google Scholar 

  • Weismann A (1889, 1891) Essays upon heredity and kindred biological problems, vol I (1st edn 1889, 2nd edn 1891). Clarendon Press, Oxford

    Google Scholar 

  • Weismann A (1892a) Aufsätze über Vererbung und verwandte biologische Fragen. Verlag von Gustav Fischer, Jena

    Google Scholar 

  • Weismann A (1892b) Essays upon heredity and kindred biological problems, vol II. Clarendon Press, Oxford

    Google Scholar 

  • Weismann A (1892c) Das Keimplasma: Eine Theorie der Verebung. Verlag von Gustav Fischer, Jena

    Google Scholar 

  • Weismann A (1913a) Vorträge über Deszendenztheorie, Vol I (3. Aufl). Verlag von Gustav Fischer, Jena

    Google Scholar 

  • Weismann A (1913b) Vorträge über Deszendenztheorie, Vol II (3. Aufl). Verlag von Gustav Fischer, Jena

    Google Scholar 

  • Williams GC (1957) Pleiotropy, natural selection and the evolution of senescence. Evolution 11:398–411

    Google Scholar 

  • Williamson AR, Askonas BA (1972) Senescence of an antibodyforming cell clone. Nature 238:337–339

    Google Scholar 

  • Witkowski JA (1980) Dr Carrel's immortal cells. Med Hist 24:129–142

    Google Scholar 

  • Woolhouse HW (1967) The nature of senescence in plants. In: Woolhouse HW (ed) Aspects of the biology of ageing. Symposia of the Society for Experimental Biology, No XXI. Cambridge University Press. Cambridge, pp 179–213

    Google Scholar 

  • Zavala C, Herner G, Fialkow PJ (1978) Evidence for selection in cultured diploid fibroblast strains. Exp Cell Res 117:137–144

    Google Scholar 

  • Zs-Nagy I (1978) A membrane hypothesis of aging. J Theor Biol 75: 189–195

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Institute for Medical Research, The Ridgeway, Mill Hill, NW7 1AA, London, England

    Thomas B. L. Kirkwood

  2. Institut für Anthropologie und Humangenetik, Universität Heidelberg, Im Neuenheimer Feld 328, D-6900, Heidelberg, Germany

    Thomas Cremer

Authors
  1. Thomas B. L. Kirkwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Cremer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kirkwood, T.B.L., Cremer, T. Cytogerontology since 1881: A reappraisal of August Weismann and a review of modern progress. Hum Genet 60, 101–121 (1982). https://doi.org/10.1007/BF00569695

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00569695

Keywords

Search

Navigation