Senescence pp 13-21 | Cite as

Senescence in Cell Culture: An Accumulation of Errors or Terminal Differentiation?

  • Vincent J. Cristofalo
Part of the Cellular Senescence and Somatic Cell Genetics book series (CSSCG, volume 2)


Senescence in cell culture represents an ideal model system to examine a variety of questions related to cellular aging. The process of aging in vitro can be followed conveniently and precisely by measurement of the saturation density of the culture (1), the percentage of clones that can proliferate (2) or the percentage of cells incorporating 3H-thymidine under a given standard set of conditions (3). In addition, other physiologic changes which parallel the losses in proliferative capacity such as the increase in lysosomes and lysosomal enzyme activity (4–6) can be conveniently studied using proliferative activity as an independent measure of population age. In these cultures, most, if not all, environmental factors can be controlled. Thus, we can design experiments to determine the answer to fundamental questions at the cellular level which could not be answered easily in vivo.


Error Theory Free Radical Reaction Amino Acid Analogue Lysosomal Enzyme Activity Ideal Model System 
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  1. 1.
    Hayflick, L. and Moorhead, P.S. 1961. The serial cultivation of human diploid cell strains. Exp. Cell Res. 25: 585.CrossRefGoogle Scholar
  2. 2.
    Merz, G.S. and Ross, J.D. 1969. Viability of human diploid cells as a function of in vitro age. J. Cell Physiol. 74: 219.PubMedCrossRefGoogle Scholar
  3. 3.
    Cristofalo, V.J. and Sharf, B.B. 1973. Cellular senescence and DNA synthesis. Thymidine incorporation as a measure of population age in human diploid cells. Exp. Cell Res. 76: 419.PubMedCrossRefGoogle Scholar
  4. 4.
    Cristofalo, V.J., Parris, N. and Kritchevsky, D. 1967. Enzyme activity during the growth and aging of human cells in vitro. J. Cell Physiol. 69 263.PubMedCrossRefGoogle Scholar
  5. 5.
    Robbins, E., Levine, E.M. and Eagle, H. 1970. Morphologic changes accompanying senescence of cultured human diploid cells. J.Exp. Med. 131: 1211.PubMedCrossRefGoogle Scholar
  6. 6.
    Lipetz, J. and Cristofalo, V.J. 1972. Ultrastructural changes accompanying the aging of human diploid cells in culture. J. Ultrastruct. Res. 39: 43.PubMedCrossRefGoogle Scholar
  7. 7.
    Holliday, R. and Tarrant, G.M. 1972. Altered enzymes in ageing human fibroblasts. Nature 238; 26.PubMedCrossRefGoogle Scholar
  8. 8.
    Lewis, C.M. and Tarrant, G.M. 1972. Error theory and ageing in human diploid fibroblasts. Nature 239: 316.PubMedCrossRefGoogle Scholar
  9. 9.
    Holliday, R., Porterfield, J.S. and Gibbs, D.D. 1974. Premature ageing and occurrence of altered enzyme in Werner’s syndrome fibroblasts. Nature 248; 762.PubMedCrossRefGoogle Scholar
  10. 10.
    Orgel, L.E. 1963. The maintenance of the accuracy of protein synthesis and its relevance to aging. Proc. Nat. Acad. Sci. USA 49: 517.PubMedCrossRefGoogle Scholar
  11. 11.
    Orgel, L.E. 1973. Ageing of clones of mammalian cells. Nature 243: 441.PubMedCrossRefGoogle Scholar
  12. 12.
    Goldstein, S. and Singal, D.P. 1974. Alteration of fibroblast gene products in vitro from a subject with Werner’s syndrome. Nature (Lond.) 251; 719.CrossRefGoogle Scholar
  13. 13.
    Goldstein, S. and Moerman, E.J. 1976. Defective proteins in normal and abnormal human fibroblasts during aging in vitro. Interdiscipl. Topics Geront. 10: 24.Google Scholar
  14. 14.
    Goldstein, S. and Moerman, E.J. 1975. Heat-labile enzymes in skin fibroblasts from subjects with progeria. New Engl. J. Med. 292: 1306.CrossRefGoogle Scholar
  15. 15.
    Pendergrass, W.R., Martin, G.M. and Bornstein, P. 1975. Evidence contrary to the protein error hypothesis for in vitro senescence. J. Cell. Physiol. 87: 3.CrossRefGoogle Scholar
  16. 16.
    Danot, M., Gershon, H. and Gershon, D. 1975. The lack of altered enzyme molecules in “senescent” mouse embryo fibroblasts in culture. Mech. Ageing Develop. 4 289.CrossRefGoogle Scholar
  17. 17.
    Holland, J.J., Kohne, D. and Doyle, M.V. 1973. Analysis of virus replication in ageing human fibroblasts cultures. Nature 245: 316.PubMedCrossRefGoogle Scholar
  18. 18.
    Tomkins, G.C., Stanbridge, E.J. and Hayflick, L. 1974. Viral probes of aging in the human diploid cell strain WI-38. Proc. Soc. Exp. Biol. Med. 146: 385.PubMedGoogle Scholar
  19. 19.
    Cristofalo, V.J. and Kabakjian, J. 1975. Lysosomal enzymes and aging in vitro: subcellular enzyme distribution and effect of hydrocortisone on cell lifespan. Mech. Ageing Develop, 4 19.CrossRefGoogle Scholar
  20. 20.
    Ryan, J.M., Duda, G. and Cristofalo, V.J. 1974. Error accumulation and aging in human diploid cells. J. Gerontol. 29: 616.PubMedGoogle Scholar
  21. 21.
    Balin, A.K., Goodman, D.B.P., Rasmussen, H. and Cristofalo, V.J. 1976. The effect of oxygen tension on the growth and metabolism of WI-38 cells. J. Cell. Physiol. 89: 235.PubMedCrossRefGoogle Scholar
  22. 22.
    Balin, A.K., Goodman, D.B.P., Rasmussen, II. and Cristofalo, V.J. 1976. The effect of oxygen and vitamin E on the lifespan of human diploid cells in vitro. Submitted for publication.Google Scholar
  23. 23.
    Packer, L. and Smith, J.R. 1974. Extension of the lifespan of cultured normal human cells by Vitamin E. Proc. Nat. Acad. Sci. USA 71 4763.PubMedCrossRefGoogle Scholar
  24. 24.
    Cristofalo, V.J. 1972. Animal cell cultures as a model system for the study of aging. Adv. Gerontol. Res. 4: 45.Google Scholar
  25. 25.
    Martin, G.M., Sprague, C.A., Norwood, T.H. and Pendergrass, W.R. 1974. Clonal selection, attenuation and differentiation in an in vitro model of hyperplasia. Am. J. Path. 74: 137.PubMedGoogle Scholar
  26. 26.
    Martin, G.M., Sprague, C.A., Norwood, T.H., Pendergrass, W.R., Bornstein, P., Hoehn, H. and Arend, W. P. 1975. Do hyperplastoid cell lines “differentiate themselves to death” in cell impairment. In Aging and Development. V.J. Cristofalo and E. Holeckova, eds. Plenum Press, N.Y. p. 67.Google Scholar
  27. 27.
    Macieria-Coelho, A., Loria, E. and Berumen, L. 1975. Relationship between cell kinetic changes and metabolic events during cell senescence in vitro in cell impairment. V.J. Cristofalo and E. Holeckova, eds. Plenum Press, N.Y. p. 51.Google Scholar
  28. 28.
    Absher, P.M., Absher, R.G. and Barnes, W.D. 1974. Genealogies of clones of diploid fibroblasts: cinemicrophotographic observations of cell division patterns in relation to population age. Exp. Cell Res. 88: 95.PubMedCrossRefGoogle Scholar
  29. 29.
    Cristofalo, V.J. and Kritchevsky, D. 1970. Cell size and nucleic acid content in the diploid human cell line WI-38 during aging. Medicinia Experimentalis 19: 313.Google Scholar
  30. 30.
    Bowman, P.D., Meek, R.L. and Daniel, C.W. 1975. Aging of human fibroblasts in vitro. Correlations between DNA synthetic ability and cell size. Exp. Cell Res. 93: 184.PubMedCrossRefGoogle Scholar
  31. 31.
    Mitsui, Y. and Schneider, E.L. 1976. Relationship between cell replication and volume in senescent human diploid fibroblasts. Mech. Ageing Develop. 5: 45.CrossRefGoogle Scholar
  32. 32.
    Ryan, J.M. and Cristofalo, V.J. 1975. Chromatin template activity during aging in WI-38 cells. Exp. Cell Res. 90: 456.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Vincent J. Cristofalo
    • 1
  1. 1.The Wistar Institute of Anatomy and BiologyPhiladelphiaUSA

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