Human Cells and the Finite Lifespan Theory

  • Thomas B. L. Kirkwood
  • Robin Holliday
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 118)


Cultures of human diploid fibroblasts are characterized by: i) finite lifespan, ii) marked heterogeneity in the growth potential of individual cells within the culture, iii) considerable variation in lifespans of parallel cultures of the same cell strain. To explain these properties, we have proposed a commitment theory of cellular aging. Cells are assumed initially to be uncommitted (potentially immortal) but, at each cell division, each daughter cell is assumed to have some fixed probability of becoming irreversibly committed to senesce and die after a specific number of cell generations. During the period between commitment and senescence, cells are assumed to multiply normally, so the uncommitted cells are diluted by committed ones and may be lost in subculturing. The theory explains features i) - iii) above and, in particular, suggests why diploid cultures have finite lifespans while transformed or permanent lines grow indefinitely. It also validly predicts the behaviour of mixed cultures of distinguishable but otherwise similar cell types, and that culture lifespan may be significantly decreased by drastic reduction of population size. The important converse prediction that culture lifespan may be extended indefinitely by growing sufficiently large cultures or by selectively isolating uncommitted cells remains to be tested.


Cellular Aging Diploid Fibroblast Human Diploid Fibroblast Cell Cycle Time Human Diploid Cell 
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  1. 1.
    Hayflick, L., Moorhead, P.S. The serial subcuitivation of human diploid cell strains. Exp. Cell Res. 25:585–621, 1961.CrossRefGoogle Scholar
  2. 2.
    Hayflick, L. The limited in vitro lifetime of human diploid cell strains. Exp. Cell Res. 37:614–636, 1965.PubMedCrossRefGoogle Scholar
  3. 3.
    Martin, G.M., Sprague, C.A., Epstein C. Replicative life-span of cultivated human cells. Lab Invest. 23:86–92, 1970.PubMedGoogle Scholar
  4. 4.
    Thompson, K.V.A. and Holliday, R. Effect of temperature on the longevity of human fibroblasts in culture. Exp. Cell Res. 80:354–360, 1973.PubMedCrossRefGoogle Scholar
  5. 5.
    Martin, G.M., Sprague, C.A., Norwood, T.H., et al. Clonal selection, attenuation and differentiation in an in vitro model of hyperplasia. Am. J. Pathol. 74:137–153, 1974.PubMedGoogle Scholar
  6. 6.
    Hayflick, L. The biology of human aging. Am. J. Med. Sci. 265:433–455, 1973.CrossRefGoogle Scholar
  7. 7.
    Smith, J.R., Hayflick, L. Variation in the life-span of clones derived from human diploid cell strains. J. Cell Biol. 62: 48–53. 1974.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith, J.R., Pereira-Smith, O.M., Schneider, E.L. Colony size distributions as a measure of in vivo and in vitro aging. Proc. Natl. Acad. Sci. USA 75:1353–1356, 1978.PubMedCrossRefGoogle Scholar
  9. 9.
    Holliday, R. Growth and death of diploid and transformed human fibroblasts. Fed. Proc. Fed. Am. Soc. Exp. Biol. 34:51–55, 1974.Google Scholar
  10. 10.
    Kirkwood, T.B.L., Holliday R. Commitment to senescence. A model for the finite and infinite growth of diploid and transformed human fibroblasts in culture. J. Theoret Biol. 53:481–496, 1975.Google Scholar
  11. 11.
    Holliday, R., Huschtscha, L.I., Tarrant, G.M., et al. Testing the commitment theory of cellular aging. Science 198:366–372, 1977.PubMedCrossRefGoogle Scholar
  12. 12.
    Kirkwood, T.B.L., Holliday, R. A stochastic model for the commitment of human cells to senescence. Biomathematics and Cell Kinetics. Edited by A.J. Valleron, P.D.M. Macdonald. Elsevier/North-Holland, Biomedical Press, 1978, pp. 161–172.Google Scholar
  13. 13.
    Jacobs J.P., Jones, C.M., Baille, J.P. Characteristics of a human diploid cell designated MRC-5. Nature 227:168–170, 1970.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • Thomas B. L. Kirkwood
    • 1
    • 2
  • Robin Holliday
    • 1
    • 2
  1. 1.National Institute for Biological Standards and ControlLondonEngland
  2. 2.National Institute for Medical ResearchLondonEngland

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