Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

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

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 to check access.

References

  1. 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

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

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

  4. 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

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

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

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

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

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

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

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

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

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

  14. 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

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

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

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

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

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

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

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

  22. 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

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

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

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

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

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

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

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

  30. 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

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

  32. 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

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

  34. 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

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

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

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

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

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

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

  41. 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

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

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

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

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

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

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

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

  49. 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

  50. 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

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

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

  53. 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

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

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

  56. 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

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

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

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

  60. 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

  61. 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

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

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

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

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

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

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

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

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

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

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

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

  73. 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

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

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

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

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

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

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

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

  81. 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)

  82. 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

  83. 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

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

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

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

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

  88. 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

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

  90. 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

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

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

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

  94. 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

  95. 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

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

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

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

  99. 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)

  100. 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

  101. 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

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

  103. 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

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

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

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

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

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

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

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

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

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

  113. 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

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

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

Download references

Author information

Correspondence to Thomas B. L. Kirkwood.

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

Keywords

  • Internal Medicine
  • Natural Selection
  • Metabolic Disease
  • Somatic Cell
  • Research Area