Aging and Changes in Genetic Information

  • R. W. Hart
  • S. P. Modak
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 129)


Although all placental mammals are characterized by similar morphological, physiological, and biochemical parameters, they differ from one another in maximum achievable life span by approximately fifty-fold (1,2). Even within closely associated families of recent evolutionary occurrence, such as the primates and Myomorph rodents, e.g., Mus musculus and Peromyscus leucopus, life spans vary by more than twenty fold (3) and three fold (4), respectively. Thus, it appears that whatever governs the life span of a species must be able to be modified rapidly. This imposes strong constraints on the possible genetic mechanisms for the evolution of longevity-assurance systems (4). Two ways by which rapid evolution of longevity could occur, and yet be consistent with basic molecular genetics, would be either via modification of already existing genetic information (species differences in longevity reflecting differences in the turning off of longevity-assurance systems during fetal development), or through slight but significant changes in a number of interlocking processes governing phenotypic expression. Either or both of these mechanisms might explain the rapid evolution of life span within species without necessitating the concurrent input of new genes.


Polycyclic Aromatic Hydrocarbon Life Span Excision Repair Xeroderma Pigmentosum Pyrimidine Dimer 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. Comfort, in:“Ageing, The Biology of Senescence,” Holt, Rinehart and Wilson, New York (1964).Google Scholar
  2. 2.
    W. Andrew, in:“The Fine Structure and Histochemical Changes in Ageing,” Academic Press, New York (1968).Google Scholar
  3. 3.
    R. G. Cutler, Exp. Gerontol. 10:37 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    G. A. Sacher and R. W. Hart, in:“Genetic Effects of Aging,” D. Bergsma and D. Harrison, eds., Alan R. Liss, New York (1978).Google Scholar
  5. 5.
    P. Burch, in:“The Fine Structure and Histochemical Changes in Ageing,” Academic Press, New York (1968).Google Scholar
  6. 6.
    C. Finch, in:“Animal Models for Biomedical Research IV“, Nat. Acad. Sci. USA, Wash., D.C. (1971).Google Scholar
  7. 7.
    N. Shock, Ann. Rev. Physiol. 23:97 (1961).CrossRefGoogle Scholar
  8. 8.
    A. Engel and R. Larsson, in:“Cancer and Aging,” Norcliska Bakhandelns Forlag, Stockholm (1978).Google Scholar
  9. 9.
    T. Makinodan, E. Perkins, and M. Chen, Adv. Gerontol. Res. 3:171 (1971).PubMedGoogle Scholar
  10. 10.
    A. G. Schwartz, Exp. Cell Res. 94:445 (1975).PubMedCrossRefGoogle Scholar
  11. 11.
    A. G. Schwartz and C. J. Moore, Exp. Cell Res. 109:448 (1977).PubMedCrossRefGoogle Scholar
  12. 12.
    E. Boyland, Biochem. Soc. Symp. 5:40 (1950).Google Scholar
  13. 13.
    P. Sims and P. L. Grover, Adv. Cancer Res. 20:165 (1975).CrossRefGoogle Scholar
  14. 14.
    M. E. Duncan and P. Brookes, Int. J. Cancer 4:813 (1970).CrossRefGoogle Scholar
  15. 15.
    E. Huberman, J. K. Selkirk, and C. Heidelberger, Cancer Res. 31:2161 (1971).PubMedGoogle Scholar
  16. 16.
    M. E. Duncan and P. Brookes, Int. J. Cancer 9:349 (1972).PubMedCrossRefGoogle Scholar
  17. 17.
    A. H. Conney, Science 178:576 (1972).PubMedCrossRefGoogle Scholar
  18. 18.
    H. V. Gelboin, F. J. Weibel, and H. Kinoshita, in:“Chemical Carcinogenesis,” P. O. P. T’so and J. A. DiPaolo, eds., Marcel Dekker, New York (1974).Google Scholar
  19. 19.
    D. W. Nebert and H. V. Gelboin, Arch. Biochem. Biophys. 134:76 (1969).PubMedCrossRefGoogle Scholar
  20. 20.
    G. Kellerman, E. Cantrell, C. R. Shaw, Cancer Res. 33:1654 (1973).Google Scholar
  21. 21.
    J. P. Whitlock and H. V. Gelboin, J. Radiol. Chem. 249: 2616 (1974).Google Scholar
  22. 22.
    J. P. Whitlock, and H. V. Gelboin, J. Biol. Chem. 248:6114 (1973).PubMedGoogle Scholar
  23. 23.
    D. W. Nebert, W. F. Benedict, J. E. Gielen, F. Oesch, and J. W. Daly, Mol. Pharmacol. 8:374 (1972).PubMedGoogle Scholar
  24. 24.
    R. E. Kouri, H. Ratrie, and C. E. Whitmore, J. Natl, Cancer Inst. 51:197 (1973).Google Scholar
  25. 25.
    F. J. Weibel, J. C. Leutz, and H. V. Belboin, Arch. Biochem. Biophys. 154:292 (1973).CrossRefGoogle Scholar
  26. 26.
    K. Burki, A. G. Liebelt, and E. Bresnick, J. Natl. Cancer Inst. 50:369 (1973).PubMedGoogle Scholar
  27. 27.
    G. Kellerman, C. R. Shaw, M. Lugten-Kellerman, N. Engl. J. Med. 289:934 (1973).CrossRefGoogle Scholar
  28. 28.
    A. Comfort, in:“Ageing, the Biology of Senescence,” Holt, Rinehart and Wilson, New York (1964).Google Scholar
  29. 29.
    R. W. Hart, and R. B. Setlow, Proc. Natl. Acad. Sci. USA 71:2169 (1974).PubMedCrossRefGoogle Scholar
  30. 30.
    D. E. Brash and R. W. Hart, J. Environ. Pathol. Toxicol. 2:79 (1978).PubMedGoogle Scholar
  31. 31.
    H. F. Stich and R. H. C. San, Proc. Soc. Exp. Biol. Med. 142:155 (1973).PubMedGoogle Scholar
  32. 32.
    J. E. Cleaver, in:“Methods in Cancer Research,” vol. 9, H. Busch, ed., Academic Press, New York (1975).Google Scholar
  33. 33.
    R. W. Hart and J. E. Trosko, Interdisc. Top. Gerontol. 9:134 (1976).Google Scholar
  34. 34.
    J. E. Cleaver and J. E. Trosko, Photochem. Photobiol. 11:547 (1970).PubMedCrossRefGoogle Scholar
  35. 35.
    J. E. Cleaver, Nature 270:451 (1977).PubMedCrossRefGoogle Scholar
  36. 36.
    R. B. Setlow, J. D. Regan, and W. L. Carrier, Biophys. Soc. Abstr. 12:19a (1972).Google Scholar
  37. 37.
    K. Hall, C. Albrightson, and R. W. Hart, XIth Internat. Cong. Gerontol., Tokyo, Japan (1978).Google Scholar
  38. 38.
    V. Paffenholz, Mech. Ageing Dev. 7:131 (1978).PubMedCrossRefGoogle Scholar
  39. 39.
    P. Cerutti, K. Shinohara, and J. Remsen, J. Toxicol. Environ. Health 2:1375 (1977).PubMedCrossRefGoogle Scholar
  40. 40.
    J. Smith-Sonneborn, personal communications (1978).Google Scholar
  41. 41.
    A. Dipple and J. J. Roberts, Biochemistry 16:1499 (1977).PubMedCrossRefGoogle Scholar
  42. 42.
    M. Ikenaga, Y. Ishii, M. Toda, T. Kakunaga, H. Takebe, and S. Kondo, in:“Molecular Mechanisms for Repair of DNA,” P. C. Hanawalt and R. B. Setlow, eds., Plenum Press, New York (1975).Google Scholar
  43. 43.
    R. Ben-Ishai, and I. Peleg, in: “Molecular Mechanisms for Repair of DNA, P. C. Hanwalt and R. B. Setlow, Plenum Press, New York (1975).Google Scholar
  44. 44.
    R. W. Hart, S. D’Ambrosio, K. J. Ng, and S. P. Modak, Mech. Ageing Dev. 9:203 (1978).CrossRefGoogle Scholar
  45. 45.
    R. W. Hart, K. Y. Hall, and F. B. Daniel, Photochem. Photobiol. 28:131 (1978).PubMedCrossRefGoogle Scholar
  46. 46.
    S. P. Modak and F. J. Bollum, Exp. Cell Res. 62:421 (1970).PubMedCrossRefGoogle Scholar
  47. 47.
    S. P. Modak and F. J. Bollum, Exp. Cell Res. 75:307 (1972).PubMedCrossRefGoogle Scholar
  48. 48.
    S. P. Modak and G. B. Price, Exp. Cell Res. 65:289 (1971).PubMedCrossRefGoogle Scholar
  49. 49.
    G. B. Price, S. P. Modak, and T. Makinodan, Science 190:917 (1971).CrossRefGoogle Scholar
  50. 50.
    H. R. Massie, M. B. Baird, and R. J. Nicolosi, Arch. Biochem. Biophys. 153:736 (1972).PubMedCrossRefGoogle Scholar
  51. 51.
    S. P. Modak, in:“Cell Differentiation,” R. Harris, P. Allen, and D. Viza, eds., Munksgaard Publications, Copenhagen (1972).Google Scholar
  52. 52.
    S. P. Modak and H. Traurig, Cell Differentiation 1:351 (1972).PubMedCrossRefGoogle Scholar
  53. 53.
    J. Piatigorsky, S. S. Rothschild, and L. M. Milstone, Dev. Biol. 34:334 (1973).PubMedCrossRefGoogle Scholar
  54. 54.
    P. Karran and M. G. Ormerod, Biochim. Biophys. Acta 299:54 (1973).PubMedGoogle Scholar
  55. 55.
    K. J. Wheeler and J. T. Lett, Proc. Natl. Acad. Sci. USA 71:1962 (1974).CrossRefGoogle Scholar
  56. 56.
    M. F. Counis, E. Chaudun, and Y. Courtois, Dev. Biol. 57:47 (1977).PubMedCrossRefGoogle Scholar
  57. 57.
    D. W. Appleby and S. P. Modak, Proc. Natl. Acad. Sci. USA 74:5579 (1977).PubMedCrossRefGoogle Scholar
  58. 58.
    S. Goldstein, N. Engl. J. Med. 285:1120 (1971).PubMedCrossRefGoogle Scholar
  59. 59.
    G. M. Hahn, D. King, and S. J. Yang, Nature 230:242 (1971).CrossRefGoogle Scholar
  60. 60.
    F. E. Stockdale, Science 171:1145 (1971).PubMedCrossRefGoogle Scholar
  61. 61.
    F. E. Stockdale and M. C. O’Neil, J. Cell Biol. 52:589 (1972).PubMedCrossRefGoogle Scholar
  62. 62.
    R. W. Hart and R. B. Setlow, Mech. Ageing Dev. 5:67 (1976).PubMedCrossRefGoogle Scholar
  63. 63.
    M. R. Mattern and P. Cerutti, Biochim. Biophys. Acta 395:48 (1975).PubMedGoogle Scholar
  64. 65.
    G. E. Milo and R. W. Hart, Arch. Biochem. Biophys. 176:324 (1976).PubMedCrossRefGoogle Scholar
  65. 66.
    A. C. Chen, S. K. C. Ng, and I. G. Walker, J. Cell Biol. 70:685 (1976).CrossRefGoogle Scholar
  66. 67.
    J. Treton, S. P. Modak, and Y. Courtois, manuscript in preparation (1978).Google Scholar
  67. 68.
    A. Ruiz-Carilio, L. J. Wangh, and V. G. Allfrey, Science 190:117 (1975).CrossRefGoogle Scholar
  68. 69.
    A. Olins and D. E. Olins, Science 183:330 (1974).PubMedCrossRefGoogle Scholar
  69. 70.
    P. Oudet, M. Gross-Bellard, and P. Chambon, Cell 4:281 (1975).PubMedCrossRefGoogle Scholar
  70. 71.
    D. R. Hewish and L. A. Burgoyne, Biochem. Biophys. Res. Comm. 52:504 (1973).PubMedCrossRefGoogle Scholar
  71. 72.
    M. Noll, Nature 251:249 (1974).PubMedCrossRefGoogle Scholar
  72. 74.
    E. M. Bradbury, in:“The Organization of Expression of Ekaryotic Genome,” E. M. Bradbury and K. Javaherian, eds., Academic Press, New York (1977).Google Scholar
  73. 75.
    R. D. Kornberg, Science 184:868 (1974).PubMedCrossRefGoogle Scholar
  74. 76.
    R. D. Kornberg and J. O. Thomas, Science 184:865 (1974).PubMedCrossRefGoogle Scholar
  75. 77.
    B. Sollner-Webb and G. Felsenfeld, Biochemistry 14:2915 (1975).PubMedCrossRefGoogle Scholar
  76. 78.
    R. Axel, H. Cedar, and G. Felsenfeld, Proc. Natl. Acad. Sci. USA 70:2921 (1975).Google Scholar
  77. 79.
    J. O. Thomas, in:“The Organization and Expression of Eukaryotic Genome,” E. M. Bradbury and K. Javaherian, eds. Academic Press, New York (1977).Google Scholar
  78. 80.
    N. R. Morris, Cell 9:627 (1976).PubMedCrossRefGoogle Scholar
  79. 81.
    B. R. Shaw, T. M. Herman, R. T. Kovacic, G. S. Beaudreau, and K. E. van Holde, Proc. Natl. Acad. Sci. USA 73:505 (1976).PubMedCrossRefGoogle Scholar
  80. 82.
    A. J. Varshavsky, V. V. Bakayev, and G. P. Georgiev, Nucleic Acids Res. 3:477 (1976).PubMedGoogle Scholar
  81. 83.
    J. P. Whitlock and R. T. Simpson, Biochemistry 15:3307 (1976).PubMedCrossRefGoogle Scholar
  82. 84.
    R. J. Wilkins and R. W. Hart, Nature 247:35 (1976).CrossRefGoogle Scholar
  83. 85.
    W. J. Bodell, Nucleic Acids Res. 4:2619 (1977).PubMedCrossRefGoogle Scholar
  84. 88.
    W. Andrew, in:“The Fine Structure and Histochemical Changes in Ageing,” Academic Press, New York (1968).Google Scholar
  85. 89.
    H. Weintraub, A. Worcel, and B. Alberts, Cell 9:409 (1978).CrossRefGoogle Scholar
  86. 90.
    A. Garel and R. Axel, Proc. Natl. Acad. Sci. USA 73:3966 (1976).PubMedCrossRefGoogle Scholar
  87. 91.
    H. Weintraub and M. Groudine, Science 193:848 (1976).PubMedCrossRefGoogle Scholar
  88. 92.
    M. J. Pythilla and F. G. Sherman, Biochem. Biophys. Res. Comm. 31:340 (1968).CrossRefGoogle Scholar
  89. 93.
    D. I. Kurtz and F. M. Sinex, Biochim. Biophys. Acta 145:840 (1967).PubMedGoogle Scholar
  90. 94.
    H. P. von Hahn, Gerontologia 16:116 (1970).CrossRefGoogle Scholar
  91. 95.
    S. M. Zhelabovskaya and G. D. Berdyshev, Exp. Gerontol. 7:313 (1972).PubMedCrossRefGoogle Scholar
  92. 96.
    D. I. Kurtz, A. P. Russel, and F. M. Sinex, Mech. Ageing Dev. 3:37 (1974).PubMedCrossRefGoogle Scholar
  93. 97.
    H. Y. Samis and V. J. Wulff, Exp. Gerontol. 4:111 (1969).PubMedCrossRefGoogle Scholar
  94. 98.
    B. T. Hill, Gerontologia 22:111 (1976).CrossRefGoogle Scholar
  95. 99.
    R. G. Cutler, Proc. Natl. Acad. Sci. USA 72:4664 (1975).PubMedCrossRefGoogle Scholar
  96. 100.
    Zh. A. Medvedev, M. N. Medvedeva, and L. I. Huschtscha Gerontology 23:334 (1977).PubMedCrossRefGoogle Scholar
  97. 101.
    Zh. A. Medvedev, M. N. Medvedeva, and L. Robson, Gerontology 24:286 (1978).PubMedCrossRefGoogle Scholar
  98. 102.
    T. Lindahl and S. Ljungquist, in:“Molecular Mechanisms for Repair of DNA,” P. C. Hanawalt and R. B. Setlow, eds., Plenum Press, New York (1975).Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • R. W. Hart
    • 1
  • S. P. Modak
  1. 1.Pharmacology and Preventive MedicineThe Ohio State University College of MedicineColumbusUSA

Personalised recommendations