Abstract
Primary cultures of diploid fibroblasts give rise to populations which have limited growth potential. In the case of human cells, their in vitro life span is usually in the range of 50–70 population doublings (Hayflick, 1965; 1977; Holliday et al., 1977). In spite of strong selective pressure when growth slows down and finally ceases, permanent lines do not emerge from these populations. Diploid rodent cultures have a much shorter in vitro life span, and permanent lines, exemplified by the mouse 3T3 strain, often take over the culture (Todaro and Green, 1963).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Arlett, C.F., and Harcourt, S.A., 1983. Variation in response to mutagens amongst normal and repair defective human cells, in: “Induced Mutagenesis”, p. 249, C.W. Lawrence, ed., Plenum Press, New York.
Barski, G. and Cassingena, R., 1963, Malignant transformation in vitro of cells from C57BL mouse normal pulmonary tissue, J. Natl. Cancer Inst., 30:865.
Cattanach, B.M., 1974, Position effect variegation in the mouse, Genet. Res. 23:291.
Clough, D.W., Kunkel, L.M. and Davidson, R.L. 1982, 5-Azacytidineinduced reactivation of a Herpes simplex thymidine kinase gene, Science, 216-70.
Cole, J., Arlett, C.F., Green, M.H.L., Lowe, J. and Muriel, W., 1983, A comparison of the agar cloning and microtitration techniques for assaying cell survival and mutation frequency in L5178Y mouse lymphoma cells. Mutat. res., 111:371.
Creusot, F., Acs, G., and Christman, J.K. 1982, Inhibition of DNA methyltransferase and induction of Friend erythroleukaemia cell differentiation by 5-azacytidine and 5-aza-2′-deoxycytidine, J. Biol. Chem., 257: 2041.
Curtis, H.J., 1966, “Biological Mechanisms of Aging”, Springfield, Illinois.
Cutler, R.G., 1982a, Longevity is determined by specific genes: testing the hypothesis, in “Testing the Theories of Aging”, p. 25, R.C. Adelman and G.S. Roth, eds. CRC Press, Boca Raton, Florida.
Cutler, R.G. 1982b, The dysdifferentiative hypothesis of mammalian aging and longevity, in “The Aging Brain: Cellular and Molecular Mechanisms of Aging in the neurons system”, p. 1, E. Giacobini, G. Filogamo, G. Giacobini and A. Vernadakis, eds., Raven Press, New York.
DeMars, E., 1974, Resistance of cultured human fibroblasts and other cells to purine and pyrimidine analogues in relation to mutagenesis detection, Mutat. Res., 24: 33.
Doerfler, W., 1981, DNA methylation-a regulatory signal in eukaryotic gene expression, J. Gen. Virol., 57:1.
Doerfler, W., 1983, DNA methylation and gene activity. Ann. Rev. Biochem., 52:93.
Flatau, E., Gonzales, F.A., Michalowsky, L.A. and Jones, P.A., 1984. DNA methylation in 5-aza-2′-deoxycytidine resistant variants of C3H 10T1/2 C18 cells, Mol. Cell. Biol., 4:2098.
Gartler, S.M. and Riggs, A.D. 1983, Mammalian X-chromosome inactivation, Ann. Rev. Genet., 17:155.
Gasson, J.C., Ryden, T. and Bourgeois, S., 1983, Role of de novo DNA methylation in the glucocorticoid resistance of a T-lymphoid cell line, Nature, 302-621.
Graves, J.A.M., 1982, 5-Azacytidine-induced re-expression of alleles on the inactive X chromosome in a hybrid mouse cell line, Exptl. Cell Res., 141:99.
Harris, M., 1982, Induction of thymidine kinase in enzyme-deficient Chinese hamster cells, Cell. 29:483.
Hayflick, L., 1965, The limited in vitro lifetime of human diploid cell strains, Exptl. Cell Res., 37:614.
Hayflick, L., 1971, The Cellular basis of human aging, in: “Handbook of the Biology of Aging,” p. 159, C. Finch and L. Hayflick, eds., Van Norstrand, Reinhold, New York.
Holliday, R., 1979, A new theory of carcinogenesis, Brit. J. Cancer, 40:513.
Holliday, R., 1984, The unsolved problem of cellular ageing, Monogr. Devel. Biol., 17:60.
Holliday, R., 1984, The biological significance of meiosis, in: “Controlling Events in Meiosis”, C.W. Evans, ed., S.E.B. Symp. 38, Cambridge University Press (in press).
Holliday, R., Huschtscha, L.I., Tarrant, G.M. and Kirkwood, T.B.L., 1977, Testing the commitment theory of cellular ageing, Science, 198:366.
Holliday, R., and Kirkwood, T.B.L., 1981, Predictions of the somatic mutation and mortalization theories of cellular ageing are contrary to experimental observations, J. Theoret. Biol., 93:627.
Holliday, R., and Pugh, J. E., 1975, DNA modification mechanism and gene activity during development, Science, 187:226.
Huschtscha, L.I., and Holliday, R., 1983, The limited and unlimited growth of SV40 transformed cells from human diploid MRC-5 fibroblasts, J. Cell Sci., 63:77.
Jahner, D., Stuhlman, H., Stewart, C.H., Haubers, K., Lohler, J., Simon, I., and Jaenisch, R., 1982, De novo methylation and expression of retroviral genomes during mouse embryogenesis, Nature (Lond.), 298:623.
Jones, P.A. and Taylor, S.M., 1981, Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells, Nucleic Acids Res., 9:2933.
Jones, P.A. and Taylor, S.M., 1982, Cellular differentiation, cytidine analogues and DNA methylation, Cell. 20:85.
Kennedy, A.R., Fox, M., Murphy, G., and Little, J.B., 1981, Relationship between X-ray exposure and malignant transformation in C3H 10T1/2 cells, Proc. Nat. Acad. Sci. U.S.A., 77:7262.
Kirkwood, T.B.L., 1980, Error propagation in intracellular information transfer, J. Theoret. Biol., 82:363.
Kirkwood, T.B.L., Rosenberger, R.F., and Holliday, R., 1984, Stability of the cellular translation process, Int. Rev. Cytol., 92:93.
Land, H., Paroda, L.F., and Weinberg, R.A. 1983, Tumorigenic conversion of primary embryo fibroblasts requires at least two co-operating oncogenes, Nature (Lond.), 304:596.
Lindop, P.J., and Rotblat, J., 1961, Shortening of life and causes of death in mice exposed to a single whole body dose of radiation, Nature (Lond.), 189:645.
Mahondas, T., Sparkes, R.S. and Shapiro, L.J., 1981, Reactivation of an inactive human X-chromosome: evidence for X-inactivation by DNA methylation, Science, 211:393.
Maynard Smith, J., 1959, A theory of ageing, Nature (Lond.), 184:959.
Maynard Smith, J., 1962, The causes of ageing. Proc. Roy. Soc. B., 157:115.
Mays-Hoopes, L.L., Brown, A. and Huang, R.C.C., 1983, Methylation and re-arrangement of mouse intracisternal A particle genes during development, aging and myeloma, Mol. Cell. Biol., 3:1371.
Neary, G.J., 1960, Ageing and radiation. Nature (Lond.), 187:10.
Newbold, R.E. and Overell, R.W., 1983, Fibroblast immortality is a prerequisite for transformation by EJc-Ha-ras oncogene, Nature (Lond.), 304:64
Ono, T. and Cutler, R.C., 1978, Age-dependent relaxation of gene repression: increase of endogenons murine leukemia virus-related and globin-related RNA in brain and livers of mice, Proc. Nat. Acad. Sci. U.S.A., 75:4431.
Orgel, L.E., 1963, The maintenance of the accuracy of protein synthesis and its relevance to ageing. Proc. Nat. Acad. Sci. U.S.A., 49:517.
Orgel, L.E., 1970, The maintenance of the accuracy of protein synthesis and its relevance to ageing; a correction. Proc. Nat. Acad. Sci. U.S.A., 67:1476.
Orgel, L.E., 1973, Ageing of clones of mammalian cells, Nature (Lond.), 243-441.
Riggs, A.D., 1975, X-inactivation, differentiation and DNA methylation. Cytogenet. and Cell Genet., 14:9.
Riggs, A.D. and Jones, P.A., 1983, 5-methyl cytosine, gene regulation and cancer, Adv. Cancer Res., 40, 1.
Sacher, G.A., 1978, Evolution of longevity and survival characteristics in mammals, in “Genetics of ageing,” p. 151, E.L. Schneider, ed., Plenum Press, New York.
Schmookler-Reis, R.J. and Goldstein, S., 1982, Variability of DNA methylation patterns during serial passage of human diploid fibroblasts, Proc. Nat. Acad. Sci, U.S.A., 79:3949.
Stewart, C.L., Stuhlmann, H., Jahner, D. and Jaenisch, R., 1982, De novo methylation, expression and infectivity of retroviral genomes introduced into embryonal carcinoma cells, Proc. Nat. Acad. Sci., U.S.A., 79:4098.
Szilard, L., 1959, On the nature of the ageing process, Proc. Nat. Acad. Sci, U.S.A., 45-30.
Taylor, S.M. and Jones, P.A., 1982, Mechanism of action of eukaryotic DNA methyl transferase: use of 5-azacytidine containing DNA, J. Mol. Biol., 162:679.
Todaro, G.H. and 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.
Wilson, V.L. and Jones, P.A., 1983a, An inhibition of DNA methylation by chemical in vitro carcinogens, Cell. 32:239.
Wilson, V.L. and Jones, P.A., 1983b, DNA methylation decreases in aging but not in immortal cells, Science, 220:1055.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1985 Springer Science+Business Media New York
About this chapter
Cite this chapter
Holliday, R. (1985). The Significance of DNA Methylation in Cellular Aging. In: Woodhead, A.D., Blackett, A.D., Hollaender, A. (eds) Molecular Biology of Aging. Basic Life Sciences, vol 35. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-2218-2_17
Download citation
DOI: https://doi.org/10.1007/978-1-4899-2218-2_17
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-2220-5
Online ISBN: 978-1-4899-2218-2
eBook Packages: Springer Book Archive