Abstract
The fidelity of protein synthesis was measured in human diploid skin fibroblasts as a function of passage level (“aging in vitro”) and physiological age of tissue donor (“aging in vivo”) using two different test systems. First, in cell-free extracts the ratio of ∆ leu/∆ phe incorporation into peptide linkage following in the latter case using cells derived from elderly normal donors and from subjects with the premature aging disorders of Hutchinson-Gilford progeria and the Werner syndrome.Similar results were obtained using a second system of intact cells whereby histidine starvation induces quantifiable satellite spots resolved by two dimensional electrophoresis on polyacrylamide gels on the acidic side of the native actin species due to substitution of the neutral amino acid glutamine for the basic histidine. In fact, error frequencies appeared to decrease during aging in vitro, likely due to selection for clonal subpopulations with the highest fidelity of protein synthesis. The only increases were seen in the intact cell system where SV40-transformed cells showed a three-to-five fold greater error frequency compared to nontransformed fibroblasts. In total, these data fail to support the error catastrophe theory of cellular aging.
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References
Buchanan, J. H., Bunn, C. L., Lappin, R. I., and Stevens, A., 1980, Accuracy of in vitro protein synthesis: Translation of polyuridylic acid by cell-free extracts of human fibroblasts, Mech. Ageing & Dev., 12:339.
Danner, D. B., Schneider, E. L., and Pitha, J., 1978, Macromolecular synthesis in human diploid fibroblasts, Exp Cell Res., 114: 63.
Davies, J., Gorini, L., and David, B., 1965, Misreading of RNA code words induced by aminoglycoside antibiotics, J. Mol. Pharmacol 1: 93.
Edelmann, P. and Gallant, J., 1977, On the translational error theory of aging, Proc. Natl. Acad Sci., 74:3396.
Gallant, G. and Palmer, L., 1979, Error propagation in viable cells, Mech. Ageing & Dev., 10:27.
Gallant, J. and Foley, D., 1980, On the causes and prevention of mistranslation. in: “Ribosomes, Structure, Function and Genetics,” G. Chambliss, G. R. Craven, J. Davies, K. Davis, L. Kahan and m. Nomura, eds., University Park Press, Baltimore.
Geissler, E., Scherneck, S., Theile, M., Herold, H. J.,Staneczetki, W., Zimmerman, W., Krause, H., Prokoph, H., Vogel, F., and Platzer, H., 1980, in: “Leukaemias, Lymphomas,and Papillomas: Comparative Aspects. Munich Symposia on Microbiology,” P. A. Bachmann, ed., Taylor and Francis Ltd., London.
Goldberg, A. L. and St. John, A. C., 1976, Intracellular protein degradation in mammalian and bacterial cells, Ann. Rev. Biochem 45: 747.
Goldstein, S., 1978, Human genetic disorders which feature accelerated aging, in: “The Genetics of Aging,” E. L. Schneider, ed., Plenum Press, New York, p. 171.
Goldstein, S. and Littlefield, J. W., 1969, Effect of insulin on conversion of glucose-C-14 to C-14–02 by normal and diabetic fibroblasts, Diabetes 18: 545.
Goldstein, S. and Moerman, E. J., 1976, Defective proteins in normal and abnormal human fibroblasts during aging in vitro, Interdiscipl. Topics Geront 10:24.
Goldstein, S., Littlefield, J. W., and Soeldner, J. S., 1969, Diabetes mellitus and aging: Diminished plating efficiency of cultured human fibroblasts, Proc. Natl. Acad Sci., 64:155.
Goldstein, S., Moerman, E. J., Soeldner, J. S., Gleason, R. E., and Barnett, D. M., 1978, Chronologic and physiologic age affect replicative lifespan of fibroblsts from diabetic, prediabetic and normal donors, Science 199: 781.
Gorini, L., 1974, streptomycin and misreading of the genetic code. in: “Ribosomes,” M. Nomura et al., eds., Cold Spring Harbor Laboratory, Long Island, New York.
Gupta, R. S. and Siminovitch, L., 1980, Diptheria toxin resistance in Chinese hamster cells: Genetic and biochemical characteristics of the mutants affected in protein synthesis, Somat Cell Genet 6: 361.
Harley, C. B., 1979, “Aging, Protein Synthesis, and Mistranslation in Cultured Human Cells,” Ph.D. Thesis, McMaster University, Hamilton, Ontario, Canada.
Harley, C. B., Pollard, J., Stanners, C. P., Chamberlain, J., and Goldstein, S., 1980, Viral transformation but not aging in-creases high level mistranslation in cultured human fibroblasts, Proc. Nati. Acad Sci., 77:1885.
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.
Hayflick, L., 1965, The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res., 37:614.
Hayflick, L., 1967, The celular basis for biological aging, in: “The Handbook of the Biology of Aging,” C. E. Finch and L. Hayflick, eds., Van Nostrand Reinhold, New York.
Jelenc, P. C. and Kurland, C. G., 1979, Nucleoside triphosphate regeneration decreases the frequency of translational errors, Proc. Natl. Acad Sci., 76:3174.
Loftfield, R. B., 1963, The frequency of errors in protein biosynthesis, Biochem J., 89: 82.
Loftfield, R. B., 1972, The mechanism of aminoacylation of transfer RNA, Prog. Nucl. Acid Res., 12:87.
Loftfield, R. B. and Vanderjagt, D., 1972, The frequency of errors in protein biosynthesis, Biochem J., 128: 1353.
Martin, G. M., Sprague, C. A., and Epstein, C. J., 1970, Replicative lifespan of cultivated human cells. Effect of donor’s age, tissue and genotype, Lab. Invest 23: 86.
Matthei, J. H. and Nirenberg, M. W., 1961, Characteristics and stabilization of RNAase-sensitive protein synthesis in E. coli extracts, Proc. Natl. Acad Sci., 47:1580.
Orgel, L. E., 1963, The maintenance of the accuracy of protein synthesis and its relevance to ageing, Proc. Natl. Acad Sci., 49:517.
Parker, J. and Friesen, J. D., 1980, ‘Two out of three’ codon reading leading to mistranslation in vivo, Mo. Gen. Genet 177:439.
Parker, J., Pollard, J. W., Friesen, J. S., and Stanners, C. P., 1978, Stuttering: High level mistranslation in animal and bacterial cells, Proc Natl. Acad Sci., 75:1091.
Pollard, J. W., Harley, C. B., Chamberlain, J. W., Goldstein, S., and Stanners, C. P., 1982, Is transformation associated with an increased error frequency in mammalian cells?, J. Biol. Chem 257:5977.
Ryan, J.M., Duda, G., and Cristofalo, V.J., 1974, Error accumula-tion and aging in human diploid cells, J. Geront 29: 616.
Schneider, E. L. and Mitsui, Y., 1976, The relationship between in vitro cellular aging and in vivo human age, Proc. Natl Acad. Sci., 73: 3584.
Shmookler Reis, R. J., 1976, Enzyme fidelity and metazoan aging, Interdiscip. Top. Geront 10:11.
Shmookler Reis, R. J., Goldstein, S., and Harley, C. B., 1980, Is cellular aging a stochastic process?, Mech. Ageing & Dev., 13:393.
Wojtyk, R. I., 1981, “The Fidelity of In Vitro Protein Synthesis and Its Implications for the Aging of Human Cells,” Ph. D. Thesis, McMaster University, Hamilton, Ontario, Canada.
Wojtyk, R., and Goldstein, S., 1980, Fidelity of protein synthesis does not decline during aging of cultured human fibroblasts, J. Cell Physiol 103: 299.
Wojtyk, R.I., and Goldstein, S., 1982, Clonal Selection of human fibroblasts: Role of protein synthetic errors, J. Cell biol 95: 704
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© 1985 Plenum Press, New York
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Goldstein, S., Wojtyk, R.I., Harley, C.B., Pollard, J.W., Chamberlain, J.W., Stanners, C.P. (1985). Protein Synthetic Fidelity in Aging Human Fibroblasts. In: Salk, D., Fujiwara, Y., Martin, G.M. (eds) Werner’s Syndrome and Human Aging. Advances in Experimental Medicine and Biology, vol 190. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-7853-2_25
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DOI: https://doi.org/10.1007/978-1-4684-7853-2_25
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