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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)

Abstract

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.

Keywords

Cellular Aging Diploid Fibroblast Human Diploid Fibroblast Cell Cycle Time Human Diploid Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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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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