Abstract
The characteristics of normal diploid cell proliferation are widely used to describe in vitro models of cellular aging. In fact, it is the predictable loss in proliferative capacity that was first used to argue that normal human fibroblast cultures could serve as a model system for the study of cellular aging. Although there are many other physiological changes that occur during the lifespan of cells in culture, the regulation of cell proliferation remains a primary target of research in this area of cell biology. There have been two general approaches taken in studying the regulation and eventual loss of proliferative capacity in normal human cells in culture. They can be broadly characterized as genetic and hormonal approaches.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Bettger, W. J., Boyce, S. T., Walthall, B. J., and Ham, R. G., 1981, Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin and dexamethasone, Proc. Natl. Acad. Sci. USA, 78:5588.
Brooks, K. M., Phillips, P. D., Carlin, C.R., and Cristofalo, V.J., 1984, EGF-dependent phosphorylation of the EGF receptor in young and senescent plasma membranes isolated from WI-38 cells, J. Cell Biol., 99:414a.
Bunn, C. L., and Tarrant, G. M., 1980, Limited lifespan in somatic cell hybrids and hybrids, Exp. Cell Res., 127:385.
Burmer, G. C., Zeigler, C. J., and Norwood, T. H., 1982, Evidence for endogenous polypeptide-mediated inhibition of cell. cycle transit in human diploid cells, J. Cell Biol., 94:187.
Carlin, C. R., Phillips, P. D., Knowles, B. B., and Cristofalo, V. J., 1983, Diminished in vitro tyrosine kinase activity of the EGF receptor of senescent human fibroblasts, Nature (London), 306:617.
Cassel, D., Pike, L. J., Grant, G. A., Krebs, E. G., and Glaser, L., 1983, Interaction of epidermal growth factor-dependent protein kinase with endogenous membrane proteins and soluble peptide substrates, J. Biol. Chem., 258:2945.
Chiger, J. L., and Kaji, H., 1983, The influence of insulin in the cell cycle of human aging cells, Exp. Gerontol., 18:375.
Clemmons, D. A., 1983, Age-dependent production of a competence factor by human fibroblasts, J. Cell. Physiol., 114:61.
Cristofalo, V. J., 1970, Metabolic aspects of aging in diploid human cells, in: “Aging in Cell and Tissue Culture,” pp. 83–119, E. Holeckova and V. J. Cristofalo, eds., Plenum Press, New York.
Cristofalo, V. J., 1973, Cellular senescence: Factors modulating cell proliferation in vitro, INSERM 27:65.
Cristofalo, V. J., Finlay, C. A., Gorman, S. D., and Phillips, P. D., 1983, Modulation of proliferative capacity as a probe of the mechanism of senescence, in: “Modern Aging Research,” Vol. 3, pp. 215–232, W. Regelson and F. M. Sintex, eds., Alan R. Liss, Inc., New York.
Cristofalo, V. J., Gorman, S. D., Finlay, C., and Phillips, P. D., 1984, Loss of responsiveness to growth factors in cell senescence, in: “Meadow Brook Conference In Aging: A Biochemical Perspective,” pp. 119–141, Academic Press, New York.
Cristofalo, V. J., Wallace, J. M., and Rosner, B. A., 1979, Glucocorticoid enhancement of proliferative activity in WI-38 cells, in: “Hormones and Cell Culture,” pp. 875–887, B. Brook, G. H. Sato, and R. Ross, eds., Cold Spring Harbor Laboratory, New York.
Croce, C. M., and Koprowski, H., 1974, Positive control of transformed phenotype in hybrids between SV40-transformed and normal human cells, Science, 184:1288.
Didinsky, J. B., and Rheinwald, J. G., 1981, Failure of hydrocortisone or growth factors to influence the senescence of fibroblasts in a new culture system for assessing replication lifespan, J. Cell. Physiol., 109:171.
Drescher-Lincoln, C. K., and Smith, J. R., 1983, Inhibition of DNA synthesis in proliferating human diploid fibroblasts by fusion with senescent cytoplasts, Exp. Cell Res., 144: 455.
Goldstein, S., and Lin, C. C., 1972, Rescue of senescent human fibroblasts by hybridization with hamster cells in vitro, Exp. Cell Res., 70:436.
Gorman, S. D., and Cristofalo, V. J., 1982, Reinitiation of cellular DNA replication in senescent WI-38 cells by simian virus 40, J. Cell Biol., 95:21a
Gorman, S. D., and Cristofalo, V. J., 1984, Evidence that senescent WI-38 cells are blocked in late G1, In Vitro, 20:281.
Grunberger, G., Zick, Y., and Gordon, P., 1984, Defect in phosphorylation of insulin receptor in cells from an insulin-resistant patient with normal insulin binding, Science, 223:932.
Harley, C. B., Goldstein, S., Posner, B. I., and Guyda, H., 1981, Decreased sensitivity of old and progeric human fibroblasts to a preparation of factors with insulin-like activity, J. Clin. Invest., 68:988.
Ide, T., Tsuji, Y., Ishibashi, S., and Mitsui, Y., 1983, Reinitiation of host DNA synthesis in senescent human diploid cells by infection with simian virus 40, Exp. Cell Res., 143:343.
Kahn, A., Meinhofer, M-C., Guillouzo, A., Cottreau, D., Baffet, G., Henry, J., and Dreyfus, J-C., 1982, Modifications of phosphoproteins and protein kinases occurring with in vitro aging of cultured human cells, Gerontology, 28:360.
Kan, M., and Yamane, I., 1982, In vitro proliferation and lifespan of human diploid fibroblasts in serum-free BSA-containing medium, J. Cell Physiol., 111:155.
Muggleton-Harris, A. L., and De Simone, D. W., 1980, Replicative potentials of various fusion products between WI-38 and SV40 transformed WI-38 cells and their components, Somatic Cell Genet., 6:689.
Nette, E. G., Sit, H. L., and King, D. W., 1982, Reactivation of DNA synthesis in aging diploid human skin fibroblasts by fusion with mouse L karyoplasts, cytoplasts and whole L cells, Mech. Ageing Dev., 18:75.
Olashaw, N. E., Kress, E. D., and Cristofalo, V. J., 1983, Thymidine triphosphate synthesis in senescent WI-38 cells, Exp. Cell Res., 149:547.
Pereira-Smith, O. M., and Smith, J. R., 1981, Expression of SV40 T antigen in finite lifespan hybrids of normal and SV40-transformed fibroblasts, Somatic Cell Genet., 7:411.
Phillips, P. D., and Cristofalo, V. J., 1980, A procedure for the serum-free growth of normal human fibroblasts, J. Tissue Culture Meth., 6:123.
Phillips, P. D., and Cristofalo, V. J., 1981, Growth regulation of WI-38 cells in a serum-free medium, Exp. Cell Res., 134: 297.
Phillips, P. D., Kuhnle, E., and Cristofalo, V. J., 1983, 125I-EGF binding ability is stable throughout the replicative lifespan of WI-38 cells, J. Cell. Physiol., 114:311.
Phillips, P. D., Kaji, K., and Cristofalo, V. J., 1984, Progressive loss of the proliferative response of senescing WI-38 cells to platelet-derived growth factor, epidermal growth factor, insulin, transferrin and dexamethasone, J. Gerontol., 39:11.
Plisko, A., and Gilchrest, B. A., 1983, Growth factor responsiveness of cultured human fibroblasts declines with age, J. Gerontol., 38:513.
Rosenberg, N., Clark, D. R., and Witte, O. N. J., 1980, Abelson marine leukemia virus mutants deficient in kinase activity and lymphoid cell transformation, J. Virol., 36:766.
Rosner, B. A., and Cristofalo, V. J., 1981, Changes in specific dexamethasone binding during aging in WI-38 cells, Endocrinology, 108:1965.
Schreiber, A. B., Libermann, T. A., Lax, I., Yarden, Y., and Schlessinger, J., 1983, Biological role of epidermal growth factor-receptor clustering, J. Biol. Chem., 258:846.
Slayback, J., Cheung, L., and Geyer, R., 1977, Comparative effects of human platelet growth factor on the growth and morphology of human fetal and adult diploid fibroblasts, Exp. Cell Res., 110:462.
Snyder, M. A., Bishop, J. M., Colby, W. W., and Levinson, A. D., 1983, Phosphorylation of tyrosine-416 is not required for the transforming properties of kinase activity of pp60v−src, Cell, 32:891.
Stanbridge, E. J., 1976, Suppression of malignancy in human cells, Nature (London), 260:17.
Stein, G. H., and Yanishevsky, R. M., 1981, Quiescent human diploid cells can inhibit entry into S phase in replicative nuclei in heterodikaryons, Proc. Natl. Acad. Sci. USA, 78:3025.
Stein, G. H., Yanishevsky, R. M., Gordon, L., and Beeson, M., 1982, Carcinogen-transformed human cells are inhibited from entry into S phase by fusion to senescent cells but cells transformed by DNA tumor viruses overcome the inhibition, Proc. Natl. Acad. Sci. USA, 79:5287.
Stein, G. H., 1983, Human diploid fibroblasts (HDF) can induce DNA synthesis in cycling HDF but not in quiescent HDF on senescent HDF, Exp. Cell Res., 144:468.
Walthall, B. J., and Ham, R. G., 1981, Multiplication of human diploid fibroblasts in a synthetic medium supplemented with EGF, insulin, and dexamethasone, Exp. Cell Res., 134:303.
Witle, O.N., Goff, S., Rosenberg, N., and Baltimore, D., 1980, A transformation-defective mutant of Abelson murine leukemia virus lacks protein kinase activity, Proc. Natl. Acad. Sci. USA, 77:4993.
Yamane, I., Kan, M., Hoshi, H., and Minamoto, Y., 1981, Primary culture of human diploid cells and its long-term transfer in a serum-free medium, Exp. Cell Res., 134:470.
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
Cristofalo, V.J., Phillips, P.D., Brooks, K.M. (1985). Cellular Senescence: Factors Modulating Cell Proliferation In Vitro . 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_15
Download citation
DOI: https://doi.org/10.1007/978-1-4899-2218-2_15
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-2220-5
Online ISBN: 978-1-4899-2218-2
eBook Packages: Springer Book Archive