Abstract
The free radical theory of aging, originally postulated by D. Harman (1956) assumes there is a single basic cause of aging which is modified by genetic and environmental factors (Harman, 1984). Oxidative free radicals, produced by normal metabolic processes, over time result in a progressive accumulation of damage that can not be fully repaired by cells. Recent work, however, suggests that cellular senescence is the result of programmed internal changes, and not accumulation of oxidative genetic damage. Results obtained by fusing different types of immortalized cells suggest that immortalization results from mutations in a small number of genes which other wise act to restrict the cell’s proliferative potential. When different types of immortalized cells were fused, some hybrids became mortal again, senesced, and died (Pereira-Smith, 1988). Thus, the phenotype of cellular senescence is dominant and immortal cells arise due to recessive changes in growth control mechanisms. During the normal aging process then, cellular control of gene expression is gradually lost. One of the mRNAs of these “senescence” genes was recently cloned and coded for fibronection, a membrane associated protein (Pereira-Smith, 1988).
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References
Aebi, H. (1984). Catalase in vitro. In: Methods of Enzymology Vol 105, ( Packer, L., ed.). Academic Press, Inc. Orlando, Florida, pp. 121–126.
Burk, R.F., Lawrence, R.A., Lane, J.M. (1980). Liver necrosis and lipid peroxidation in the rat as a result of paraquat and diaquat administration: Effects of selenium deficiency. J Clin Invest 65, 1024–1031.
Chakrabarty, S., Brattain, M.G., Ochs, R.L., and Varani, J. (1987). Modulation of fibronectin, laminin, and cellular adhesion in the transformation and differentiation of murine AKR fibroblasts. J Cell Physiol. 133, 415–425.
Chandrasekhar, S., and Millis, A.J.T. (1980). Fibronectin from aged fibroblasts is defective in promoting adhesion. J Cell Physiol 103, 47–54.
Elroy-Stein, O., Bernstein, Y., and Groner, Y. (1986). Overproduction of human Cu/Zn superoxide dismutase in transfected cells. EMBO J 5, 615–622.
Flohe, L., and Gunzler, W.A. (1984). Assays of glutathione peroxidase. In: Methods of Enzymology Vol 105, ( Packer, L., ed.). Academic Press, Inc. Orlando, Florida, pp. 114–121.
Flohe, L., and Otting, F. (1984). Superoxide dismutase assays. In: Methods of Enzymology Vol 105, ( Packer, L., ed.). Academic Press, Inc. Orlando, Florida,pp. 93–104.
Graham, F.L., and Van der Eb, A.J. (1973). A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52, 456–67.
Habig, W.H., Pabst, M.J., and Jakoby, W.B. (1974). Glutathione S-transferases. J Biol Chem 249, 7130–7139.
Harman, D. (1956). Aging: A theory based on free radical and radiation chemistry. J Gerontol 11, 298–300.
Harman, D. (1984). Free radical theory of aging. Age 7, 111–131.
Hayman, E.G., Engvall, E., and Ruoslahti, E. (1981). Concomitant loss of cell surface laminin and fibronectin from transformed rat kidney cells. J Cell Biol 88, 352–357.
Johansson, L.H., and Hakan Borg, L.A. (1988). A spectrophotometric method for determination of catalase activity in small tissue samples. Anal Biochem 174, 331–336.
Keiner, M.J., McMorris, T.C., Beck, W.T., Zamora, J.M., and Taetle, R. (1987). Preclinical evaluation of illudins as anticancer agents. Cancer Research 47, 3186–9.
Krall, J., Bagley, A.C., Mullenbach, G.T., Hallewell, R.A., and Lynch, R.E. (1988). Superoxide mediates the toxicity of paraquat for cultured mammalian cells. J Biol Chem 263, 19190–1914.
Maceiera-Coelho, A., and Lima, L. (1973). Aging in vitro: Incorporation of RNA and protein precursors and acid phosphatase activity during the life span of chick embryo fibroblasts. Mech Ageing Dev 2, 13–18.
Macieira-Coelho, A., Ponten, J., Philipson, L. (1966). Inhibition of the division cycle in confluent cultures of human fibroblasts in vitro. Exp Cell Res 43, 20–29.
McCord, J., and Fridovich, I. (1969). Superoxide dismutase: An enzymatic function for erythrocuprein. J Biol Chem 244, 6049–6055.
Pereira-Smith, O.M., and Smith, J.R. (1988). Genetic analysis of indefinite division in human cells: Identification of four complementation groups. Proc Natl Acad Sci USA 85, 6042–6046
Pereira-Smith, O.M., and Smith, J.R. (1988). Are Aging and Death Programmed in our genes? Science 242, 33.
Smith, H.S., Riggs, J.L., and Mosessan, M.W. (1981). Production of fibronectin by human epithelial cells in culture. Cancer Res 39, 4138–4144.
Sorrentino, J.A., and Millis, A.J.T. (1984). Structural comparisons of fibronectins isolated from early and late passage cells. Mech Ageing Dev 28, 83–97.
Speier, C., Baker, S.S., and Newburger, P.E. (1985). Relationships between in vitro selenium supply, glutathione peroxidase activity, and phagocytic function in the HL-60 human myeloid cell line. J Biol Chem 260, 8951–8955.
Spitz, D.R., and Oberley, L.W. (1989). An assay for superoxide dismutase activity in mammalian tissue homogenates. Anal Biochem 179, 8–18.
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© 1991 Plenum Press, New York
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Kelner, M.J., Bagnell, R. (1991). Alteration of Growth Rate and Fibronectin by Imbalances in Superoxide Dismutase and Glutathione Peroxidase Activity. In: Witmer, C.M., Snyder, R.R., Jollow, D.J., Kalf, G.F., Kocsis, J.J., Sipes, I.G. (eds) Biological Reactive Intermediates IV. Advances in Experimental Medicine and Biology, vol 283. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5877-0_37
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DOI: https://doi.org/10.1007/978-1-4684-5877-0_37
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