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Molecular Genetic Approaches to Mechanisms of Senescence

  • Samuel Goldstein

Abstract

Aging research is entering its vernal epoch. The convergence of powerful techniques and advanced concepts now enables scientists to pose incisive questions at both the cellular and molecular levels. Nonetheless, the intrinsic complexity of biological aging coupled with the diversity of animal systems and their component cells tempers our zeal to discover cause and effect.

Keywords

Senescent Cell Replicative Senescence Gene Methylation Werner Syndrome Human Diploid Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Baker, S. J., Fearon, E. R., Nigro, J. M., Hamilton, S. R., Preisinger, A. C., Jessup, J. M., vanTuinen, P., Ledbetter, D. H., Barker, D. F., Nakamura, Y., White, R., & Vogelstein, B. (1989). Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science, 244, 217–221.PubMedCrossRefGoogle Scholar
  2. Brawerman, G. (1987). Determinants of messenger RNA stability. Cell, 48, 5–6.PubMedCrossRefGoogle Scholar
  3. Buckler, A. J., Vie, H., Sonenshein, G. E., & Miller, R. A. (1988). Defective T lymphocytes in old mice. Journal of Immunology, 140, 2442–2446.Google Scholar
  4. Busbee, D., Sylvia, V., Curtin, G., Peng, S., Srivastava, V., & Tilley, R. (1989a). Age-related changes in DNA polymerase α expression. Experimental Gerontology, 24:395–414.PubMedCrossRefGoogle Scholar
  5. Busbee, D. L., Sylvia, V. L., & Curtin, G. M. (1989b). Age-related differences in DNA polymerase alpha specific activity: Potential for interaction in DNA repair. In (H. Warner & E. Wang (Eds.), Growth control during cell aging. Boca Raton, FL: CRC Press, pp. 65–87.Google Scholar
  6. Butler, J. A., Heydari, A. R., & Richardson, A. (1989). Analysis of effect of age on synthesis of specific proteins by hepatocytes. Journal of Cellular Physiology, 141, 400–409.PubMedCrossRefGoogle Scholar
  7. Cedar, H. (1988). DNA methylation and gene activity. Cell, 53, 3–4.PubMedCrossRefGoogle Scholar
  8. Chang, Z-F., & Chen, K. Y. (1988). Regulation of ornithine decarboxylase and other cell cycle-dependent genes during senescence of IMR-90 human diploid fibroblasts. Journal of Biological Chemistry263, 11431–11435.PubMedGoogle Scholar
  9. Chatterjee, B., & Roy, A. K. (1990). The senescence marker protein (SMP-2) of the rat liver: purification, immunochemcial characterization, and age-dependent regulation. Biochim. Biophys. Acta.Google Scholar
  10. Chatterjee, B., Majumdar, D., Ozbilen, O., Ramana Murty, C. V., & Roy, A. K. (1987). Molecular cloning and characterization of cDNA for androgen-repressible rat liver protein, SMP-2. Journal of Biological Chemistry, 262, 822–825.PubMedGoogle Scholar
  11. Chatterjee, B., Fernandes, G., Yu, B. P., Song, C, Kim, J. M., Demyan, W., & Roy, A. K. (1989). Calorie restriction delays age-dependent loss in androgen responsiveness of the rat liver. FASEB Journal, 3, 169–173.PubMedGoogle Scholar
  12. Chau, V., Tobias, J. W., Bachmair, A., Marriott, D., Ecker, D. J., Gonda, D. K., & Varshavsky, A. (1989). Science, 243, 1576–1581.PubMedCrossRefGoogle Scholar
  13. Chiang, H-L, Terlecky, S. R., Plant, C. P., Dice, J. F. (1989). A role for a 70-kilodaton heat shock protein in lysosomal degradation of intracellular proteins. Science, 246, 382–385.PubMedCrossRefGoogle Scholar
  14. Chelly, J., Concordet, J-P., Kaplan, J-C., & Kahn, A. (1989). Illegitimate transcription: Transcription of any gene in any cell type. Proceedings of the National Academy of Science USA, 86, 2617–2621.CrossRefGoogle Scholar
  15. Cristofalo, V. J., Doggett, D. L., Brooks, K. M., Gianciarulo, F. L., & Phillips, P. D. (1989). Gene expression in cellular senescence. Gerontologist, 29, 132A.Google Scholar
  16. Dice, J. F. (1989). Altered intracellular protein degradation in aging: a possible cause of proliferative arrest. Experimental Gerontology 24:451–460.PubMedCrossRefGoogle Scholar
  17. Dice, J. F., & Goff, S. A. (1987). Error catastrophe and aging: Future directions of research. In H. R. Warner et al. (Eds.), Modern biological theories of aging (pp. 155–168). New York: Raven Press.Google Scholar
  18. Fry, M., Silber, J. M., Loeb, L. A., & Martin, G. M. (1984). Delayed and reduced cell replication and diminishing levels of DNA polymerase alpha in regenerating liver of aging mice. Journal of Cellular Physiology, 181, 225.CrossRefGoogle Scholar
  19. Gardiner-Garden, M., & Frommer, M. (1987). CpG islands in vertebrate genomes. Journal of Molecular Biology, 196, 261–282.PubMedCrossRefGoogle Scholar
  20. Goldstein, S. (1989). Cellular senescence. In L. J. Degroot, G. F. Cahill Jr., W. D. Odell, L. Martini, J. T. Potts Jr., D. H. Nelson, E. Steinberger, & A. I. Winegrad (Eds.), Endocrinology (2nd ed., pp. 2525–2549). New York: Grune & Stratton.Google Scholar
  21. Goldstein, S. (1990). Replicative senescene: The human fibroblast comes of age. Science, 249, in press.Google Scholar
  22. Goldstein, S., & Shmookler Reis, R. J. (1984). Genetic modifications during cellular aging. Molecular & Cellular Biochemistry, 64, 15–30.CrossRefGoogle Scholar
  23. Goldstein, S., & Shmookler Reis, R. J. (1985). Methylation patterns in the gene for the alpha subunit of chorionic gonadotropin are inherited with variable fidelity in clonal lineages of human fibroblasts. Nucleic Acids Research, 19, 7055–7065.CrossRefGoogle Scholar
  24. Goldstein, S., Murano, S., Benes, H., Moerman, E., Jones, R., Thweatt, R., Shmookler Reis, R. J., & Howard, B. H. (1989). Studies on the molecular-genetic basis of replicative senescene in Werner Syndrome and normal fibroblasts. Experimental Gerontology 24:461–468.PubMedCrossRefGoogle Scholar
  25. Goldstein, S., Jones, R.A., Hardin, J. W., Braunstein, G. D., & Shmookler Reis, R. J. (1990). Expression of α — and β-human chorionic gonadotropin subunits in cultured human cells. In Vitro Cellular & Developmental Biology, in press.Google Scholar
  26. Goldstein, S., Moerman, E. J., Hampton, L. L., Thorgeirsson, S. S., & Wirth, P. J. (1990). Altered polypeptide expression during replicative senescence of human diploid fibroblasts (submitted).Google Scholar
  27. Greider, C. W., & Blackburn, E. H. (1989). A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature, 337, 331–337.PubMedCrossRefGoogle Scholar
  28. Hanahan, D. (1989). Transgenic mice as probes into complex systems. Science, 246, 1265–1275.PubMedCrossRefGoogle Scholar
  29. Handeli, S., Klar, A., Meuth, M., & Cedar, H. (1989). Mapping replication units in animal cells. Cell, 57, 909–920.PubMedCrossRefGoogle Scholar
  30. Harley, C. B., Futcher, A. B., & Greider, C. W. (1990). Telomeres shorten during aging of human fibroblasts. Nature, 345, 458–460.PubMedCrossRefGoogle Scholar
  31. Hornsby, P. J., Ryan, R. F., & Cheng, C. Y. (1989). Replicative senescence and differentiated gene expression in cultured adrenocortical cells. Experimental Gerontology, 24:539–558.PubMedCrossRefGoogle Scholar
  32. Horowitz, J. M., Yandell, D. W., Park, S-H, Canning, S., Whyte, P., Buchkovich, K., Harlow, E., Weinberg, R. A., & Dryja, T. P. (1989). Point mutational inactivation of the retinoblastoma antioncogene. Science, 243, 937–940.PubMedCrossRefGoogle Scholar
  33. Huberman, J. A. (1987). Eukaryotic DNA replication: A complex picture partially clarified. Cell, 48, 7–8.PubMedCrossRefGoogle Scholar
  34. Kozak, M. (1988). A profusion of controls. Journal of Cellular Biology, 107, 1–7.CrossRefGoogle Scholar
  35. Labat-Robert, J., & Robert, L. Aging of the extracellular matrix and its pathology. Experimental Gerontology, 23, 5–18.Google Scholar
  36. Laskey, R. A., Fairman, M. P., & Blow, J. J. (1989). S phase of the cell cycle. Science, 246, 609–614.PubMedCrossRefGoogle Scholar
  37. Li, D-D., Chien, Y-K., Gu, M-Z., Richardson, A., & Cheung, H. T. (1988). Life Science, 43, 1215–1222.CrossRefGoogle Scholar
  38. Lincoln, D. W., Braunschweiger, K. L, Braunschweiger, W. R., & Smith, J. R. (1984). The two-dimensional polypeptide profile of terminally non-dividing human diploid cells. Experimental Cell Research, 154, 136–146.PubMedCrossRefGoogle Scholar
  39. Lumpkin, C. K., Jr., McClung, J. K., Pereira-Smith, O. M., & Smith, J. R. (1986). Existence of high abundance antiproliferative mRNA’s in senescent human diploid fibroblasts. Science, 232, 393–395.PubMedCrossRefGoogle Scholar
  40. Lundblad, V., & Szostak, J. W. (1989). A mutant with a defect in telomere elongation leads to senescence in yeast. Cell, 57, 633–643.PubMedCrossRefGoogle Scholar
  41. Mann, D. M., McKeown-Longo, P. J., & Millis, A.J.T. (1988). Binding of soluble fibronectin and its subsequent incorporation into the extracellular matrix by early and late passage human skin fibroblasts. Journal of Biological Chemistry, 263, 2756–2760.PubMedGoogle Scholar
  42. Millis, A.J.T., Sottile, J., Hoyle, M., Mann, D. M., & Diemer, V. (1989). Collagenase production by early and late passage cultures of human fibroblasts. Experimental Gerontology, 24, 559–576.PubMedCrossRefGoogle Scholar
  43. Millis, A.J.T., & Mann, D. M. (1989). Fibronectin and aging. In S. Carsons (Ed.), Fibronectin in health and disease. Boca Raton, FL: CRC Press.Google Scholar
  44. Murray, V. (1981). Properties of DNA polymerases from young and ageing human fibroblasts. Mechanisms of Ageing and Development, 16, 327–343.PubMedCrossRefGoogle Scholar
  45. Murty, C. V. Ramana, Mancini, M. A., Chatterjee, B., & Roy, A. K. (1988). Changes in transcriptional activity and matrix association of α2u-globulin gene family in the rat liver during maturation and aging. Biochim. Biophys. Acta, 949, 27–34.PubMedCrossRefGoogle Scholar
  46. Norwood, T. H., & Smith, J. R. (1985). The cultured fibroblast-like cell as a model for the study of aging. In (C. E. Finch & E. L. Schneider (Eds.), Handbook of the biology of aging (pp. 291–321). New York: Van Nostrand Reinhold.Google Scholar
  47. Oliver, C. N., Ahn, B-W., Moerman, E. J., Goldstein, S., & Stadtman, E. R. (1987). Age-related changes in oxidized proteins. Journal of Biological Chemistry, 262, 5488–5491.PubMedGoogle Scholar
  48. Olovnikov, A. M. (1973). A theory of marginotomy: The incomplete copying of template margin in engymic synthesis of polynucleotides and biological significance of the phenomenon. Journal of Theoretical Biology, 41, 181–190.PubMedCrossRefGoogle Scholar
  49. Pardee, A. B. (1989). G1 events and regulation of cell proliferation. Science, 246, 603–608.PubMedCrossRefGoogle Scholar
  50. Pendergrass, W., Angello, J., & Norwood, T. H. (1989). The relationship between cell size, the activity of DNA polymerase α and proliferative activity in human diploid fibroblast-like cell cultures. Experimental Gerontology, 24, 383–394.PubMedCrossRefGoogle Scholar
  51. Pfeifer, G. P., Steigerwald, S. D., Mueller, P. R., Wold, B., & Riggs, A. D. (1989). Science, 246, 810–813.PubMedCrossRefGoogle Scholar
  52. Porter, M. B., & Smith, J. R. (1989). Novel monoclonal antibodies identify an altered fibronectin molecule in senescent cells. Gerontologist, 29, 185A.Google Scholar
  53. Rechsteiner, M. (1987). Ubiquitin-mediated pathways for intracellular proteolysis. Annual Review of Cell Biology, 3, 1–30.PubMedCrossRefGoogle Scholar
  54. Riabowol, K. T., Vosatka, R. J., Ziff, E. B., Lamb, N. J., & Feramisco, J. R. (1988). Microinjection of fos-specific antibodies blacks DNA synthesis in fibroblast cells. Molecular & Cellular Biology, 8, 1670–1676.Google Scholar
  55. Richardson, A., Butler, J. A., Rutherford, M. S., Semsei, I., Gu, M. Z., Fernandes, G., & Chiang, W-H (1987). Effect of age and dietary restriction on the expression of α2u-globulin. Journal of Biological Chemistry, 262, 1–5.Google Scholar
  56. Rittling, S. R., Brooks, K. M., Cristofalo, V. J., & Baserga, R. (1986). Expression of cell cycle-dependent genes in young and senescent WI-38 fibroblasts. Proceedings of The National Academy of Sciences USA, 83, 3316–3320.CrossRefGoogle Scholar
  57. Rivett, A. J. (1989). High molecular mass intracellular proteases. Biochemistry Journal263, 625–633.Google Scholar
  58. Rothstein, M. (1982). Enzymes and altered proteins. In Biochemical approaches to aging (pp. 213–255). New York: Academic Press.CrossRefGoogle Scholar
  59. Roy, A. K., & Chatterjee, B. (1988). Altered hormone responsiveness of target genes in the rat liver during aging. In Crossroads in aging (pp. 73–90). London: Academic Press.Google Scholar
  60. Sarkar, G., & Sommer, S.S. (1989). Access to a messenger RNA sequence or its protein product is not limited by tissue or species specificity. Science, 244, 331–334.PubMedCrossRefGoogle Scholar
  61. Semsei, I., Rao, G., & Richardson, A. (1989). Changes in the expression of superoxide dismutase and catalase as a function of age and dietary restriction. Biochemical & Biophysical Research Communications.Google Scholar
  62. Seshadri, T., & Campisi, J. (1990). Suppression of c-fos transcription is part of an altered pattern of gene expression associated with senescence in human fibroblasts. Science, 247:205–209.PubMedCrossRefGoogle Scholar
  63. Shmookler Reis, R. J., Moerman, E., & Goldstein, S. (1989). DNA methylation, maintenance CpG-methylase, and senescence. In H. Warner & E. Wang (Eds.), Growth control during cell aging (pp. 191–202). Boca Raton, FL: CRC Press.Google Scholar
  64. Shmookler Reis, R. J., Finn, G. K., Smith, K., & Goldstein, S. (1990). Clonal variation in gene methylation: c-H-ras and α-hCG regions vary independently in human fibroblast lineages. Mutat. Res., 237:45–57.PubMedCrossRefGoogle Scholar
  65. Sierra, F., Fey, G. H., & Guigoz, Y. (1989). T-kininogen gene expression is induced during aging. Molecular & Cellular Biology, 9, 5610–5616.Google Scholar
  66. Silber, J. R., Fry, M., Martin, G. M„ & Loeb, L. A. (1985). Fidelity of DNA polymerases isolated from regenerating liver chromatin of aging Mus musculus. Journal of Biological Chemistry, 260, 1304–1310.Google Scholar
  67. Song, C-S., Kim, J. M., Roy, A. K., & Chatterjee, B. (1990). Structure and regulation of the senescence marker protein (SMP-2) gene promoter. Biochemistry, 29:542–551.PubMedCrossRefGoogle Scholar
  68. Sottile, J., Mann, D. M., Diemer, V., & Millis, A.J.T. (1989). Regulation of collagenase and collagenase mRNA production in early- and late-passage human diploid fibroblasts. Journal of Cellular Physiology, 138, 281–290.PubMedCrossRefGoogle Scholar
  69. Stein, G. H. (1989). Inhibitors of DNA synthesis in senescent and quiescent human diploid fibroblasts. In H. Warner & E. Wang (Eds.), Growth control during cell aging. Boca Raton, FL: CRC Press, pp. 137–147.Google Scholar
  70. Swisshelm, K., Disteche, C. M., Thorvaldsen, J., Nelson, A., & Salk, D. (1990a). Age-related increase in methylation of ribosomal genes and inactivation of chromosome-specific rRNA gene clusters in mouse. Mutation Research (in press).Google Scholar
  71. Swisshelm, K., & Salk, D. (1990b). Decreased nuclease sensitivity and transcription rate in ribosomal genes of aging mice. Mutation Research ms, (in revision).Google Scholar
  72. Turker, M. S., Swisshelm, K., Smith, A. C, & Martin, G. M. (1989). A partial methylation profile for a CpG site is stably maintained in mammalian tissues and cultured cell lines. Journal of Biological Chemistry, 264, 11632–11636.PubMedGoogle Scholar
  73. Wahba, A. J., & Dholakia, J. N. (1989). Measuring eukaryotic gene expression in vitro: Translation assays. Boca Raton, FL: CRC Press.Google Scholar
  74. Wang, E. (1989a). Statin, a nonproliferation-specific protein, is associated with the nuclear envelope and is heterogeneously distributed in cells leaving quiescent state. Journal of Cellular Physiology, 140.Google Scholar
  75. Wang, E. (1989b). The senescent stage of human fibroblasts can be identified by programmed gene expression of statin and terminin. Gerontologist, 29, 132A.Google Scholar
  76. Wang, E., Moutsatsos, I. K., & Nakamura, T. (1989). Cloning and molecular characterization of a cDNA clone to statin, a protein specifically expressed in nonproliferating quiescent and senescent fibroblasts. Experimental Gerontology, 24, 485–500.PubMedCrossRefGoogle Scholar
  77. West, M. D., Pereira-Smith, O. M., & Smith, J. R. (1989). Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity. Experimental Cell Research, 184, 138–147.PubMedCrossRefGoogle Scholar
  78. Wright, W. E., Pereira-Smith, O. M., Shay, J. W. (1989). Reversible cellular senescene: Implications for immortalization of normal human diploid fibroblasts. Molecular & Cellular Biology, 9, 3088–3092.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Samuel Goldstein
    • 1
  1. 1.John L. McClellan Memorial Veterans HospitalUniversity of Arkansas for Medical SciencesUSA

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