Alterations in Chromatin Functions during Aging in Vitro

  • Jon M. Ryan
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 53)


Changes in the metabolism of the human diploid cell line WI-38 during the aging process have been extensively characterized. For example, studies have shown age-associated increases in glycogen content (1), lipid synthesis (2), lipid content (3), the number of lysosomes (4,5) and the specific activities of lysosomal enzymes (6–8). In addition, age related decreases in the specific activities of transketolase and 6-phosphogluconate dehydrogenase have also been reported (9). If these age-related changes represent the phenotype of fundamental changes in the expression of the cellular genome, then alterations in chromatin functions could underlie the modulation of the aging process. In this regard, the metabolic alterations mentioned earlier may only reflect functional changes as they occur within the cellular chromatin. However, few reports have been published on age-associated alterations in chromatin functions.


Histone Acetylation Histone Protein Young Cell Human Diploid Cell Template Activity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cristofalo, V.J.,. Howard, B.V. and Kritchevsky, D. 1970. The biochemistry of human cells in culture. In: Organic Biologi cal and Medicinal Chemistry. U. Gallo and L. Santamaria, eds North Holland Publ., Amsterdam, 2: 95.Google Scholar
  2. 2.
    Rothblat, G., Boyd, R. and Deal, C. 1971. Cholesterol biosyn thesis in WI-38 and WI-38VA13A tissue culture cells. Exp. Cell Res. 67: 436.PubMedCrossRefGoogle Scholar
  3. 3.
    Kritchevsky, D8 and Howard, B.V. 1966. The lipids of human diploid cell strain WI-38. Ann. Med. Exp. Biol. Fenn 44: 343.Google Scholar
  4. 4.
    Lipetz, J. and Cristofalo, V.J. 1972. Ultrastructural change accompanying the aging of human diploid cells in culture. J. Ultrastr. Res. 39: 43.CrossRefGoogle Scholar
  5. 5.
    Robbins, E.5 Levine, E.M. and Eagle, H. 1970. Morphologic changes accompanying senescence of cultured human diploid cells. J. Exp. Med. 131: 1211.Google Scholar
  6. 6.
    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
  7. 7.
    Wang, K.M., Rose, N.R., Bartholomew, E.A., Balzer, M., Berde, K. and Foldvary, M. 1970. Changes of enzyme activities in human diploid cell line WI-38 at various passages. Exp. Cell Res. 61: 357.PubMedCrossRefGoogle Scholar
  8. 8.
    Milisauskas, V. and Rose, N.R. 1973. Immunochemical quanti tation of enzymes in human diploid cell line WI-38. Exp. Cell Res. 81: 279.PubMedCrossRefGoogle Scholar
  9. 9.
    Cristofalo, V.J. 1970. Metabolic aspects of aging in diploid human cells. In: Aging in Cell and Tissue Culture. E. Holeckova and V.J. Cristofalo, eds., Plenum Press, New York, p. 83.CrossRefGoogle Scholar
  10. 10.
    Comings, D.E. 1972. The structure and function of chromatin. Advances in Human Genetics 3: 237.Google Scholar
  11. 11.
    Gurley, L.R. and Hardin, J.M. 1968. The metabolism of histone fractions. I. Synthesis of histone fractions during the life cycle of mammalian cells. Arch. Biochem. Biophys. 128: 285.Google Scholar
  12. 12.
    Butler, W.B. and Mueller, G.C. 1973. Control of histone syn thesis in HeLa cells. Biochim. Biophys. Acta 294: 481.PubMedCrossRefGoogle Scholar
  13. 13.
    Shepherd, G.R., Noland, B.J. and Hardin, J.M. 1971. Histone phosphorylation in synchronized mammalian cell cultures. Arch. Biochem. Biophys. 142: 299.PubMedCrossRefGoogle Scholar
  14. 14.
    Borun, T.W., Pearson, D. and Paik, W.K. 1972. Studies of histone methylation during the HeLa S-3 cell cycle. J. Biol. Chem. 247: 4288.PubMedGoogle Scholar
  15. 15.
    Shepherd, G.R., Noland, B.J. and Hardin, J.M. 1971. Histone acetylation in synchronized mammalian cell cultures. Biochim. Biophys. Acta 228: 544.PubMedCrossRefGoogle Scholar
  16. 16.
    Rail, S.C. and Cole, R.D. 1971. Amino acid sequence and sequence variability of the amino-terminal regions of lysine-rich histones. J. Biol. Chem. 246: 7175.Google Scholar
  17. 17.
    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
  18. 18c.
    Levine, E.M. 1972. Mycoplasma contamination of animal cell cultures: A simple, rapid detection method. Exp. Cell Res. 74: 99.PubMedCrossRefGoogle Scholar
  19. 19.
    Shepherd, G.R., Noland, B.J. and Roberts, C.N. 1970. Phos phorus in histones. Biochim. Biophys. Acta 199: 265.PubMedCrossRefGoogle Scholar
  20. 20.
    Volkin, E. and Cohn, W.E. 1954. Estimation of nucleic acids.In: Methods of Biochemical Analysis 1. D. Glick, ed., Inter-science Publishers, p. 287.CrossRefGoogle Scholar
  21. 21.
    Augenlicht, L.H. and Baserga, R, 1973. Preparation and partial fractionation of nonhistone chromosomal proteins from human diploid fibroblasts. Arch. Biochem. Biophys. 158: 89*Google Scholar
  22. 22.
    Rovera, G0, Farber, J. and Baserga, R. 1971. Gene activation in WI-38 fibroblasts stimulated to proliferate. Requirement for protein synthesis. Proc. Nat. Acad. Sci. 68; 1725.Google Scholar
  23. 23.
    Tsai, R.L. and Green, H. 1973. Rate of RNA synthesis in ghost monolayers obtained from fibroblasts preparing for division. Nature New Biol. 243: 168.PubMedCrossRefGoogle Scholar
  24. 24.
    Ryan, J.M. and Cristofalo, V.J. 1972. Histone acetylation during aging of human cells in culture. Biochem. Biophys. Res. Comm. 48: 735.PubMedCrossRefGoogle Scholar
  25. 25.
    Pogo, B.G.T*, Allfrey, V.G. and Mirsky, A.E. 1966* RNA synthesis and histone acetylation during the course of gene activation in lymphocytes. Proc. Nat. Acad. Sci, J55: 805.Google Scholar
  26. 26.
    Srivastava, B.I.S. 1973. Changes in enzymic activity during cultivation of human cells in vitro. Exp. Cell Res. 80: 305.PubMedCrossRefGoogle Scholar
  27. 27.
    Butterworth, P.H., Cox, R.F. and Chesterton, C.J. 1971. Transcription of mammalian chromatin by mammalian DNA-dependent RNA polymerase. Europ. J. Biochem. 23: 229.PubMedCrossRefGoogle Scholar
  28. 28.
    Keshgegian, A.A. and Furth, J.J. 1972. Comparison of tran scription of chromatin by calf thymus and E. coli RNA polymerases. Biochem. Biophys. Res. Comm. 48: 757.CrossRefGoogle Scholar
  29. 29.
    Farber, J., Rovera, G. and Baserga, R. 1971. Template activity of chromatin during stimulation of cellular proliferation in human diploid fibroblasts. Biochem. J. 122: 189PubMedGoogle Scholar
  30. 30.
    Costlow, H. and Baserga, R. 1973. Changes in membrane transport function in Gn and G cells. J. Cell Physiol. 82: 411.PubMedCrossRefGoogle Scholar
  31. 31.
    Yanishevsky, R., Mendelsohn, M.L., Mayall, B.H. and Cristofalo, V.J. 1974. Proliferative capacity and DNA content of aging human diploid cells in culture: a cytophotometrie analysis. J. Cell. Physiol., in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1975

Authors and Affiliations

  • Jon M. Ryan
    • 1
  1. 1.The Wistar Institute of Anatomy and BiologyPhiladelphiaUSA

Personalised recommendations