Genetic, Developmental, and Evolutionary Aspects of Life Span

  • Jorge J. Yunis
  • Leonard J. Greenberg
  • Edmond J. Yunis
Part of the Comprehensive Immunology book series (COMIMUN, volume 1)


In a broad sense, life span and aging can be defined as the length of survival and the collective changes that occur during the period between conception and death (Buerger, 1957). Like most biological phenomena, there is ample evidence to support both genetic and environmental approaches to the study of life span and aging (Comfort, 1974). Although life, aging, and death are generally accepted as essential to the evolutionary process, little is known about the factors controlling the life span of a species at the phenotypic level. As a consequence, numerous theories have been proposed to explain the aging process. These theories have implicated biological clocks (Landahl, 1959; Burnet, 1973), the waning of immunologic vigor (Ram, 1967; Walford, 1969; Greenberg and Yunis, 1972), the finite lifetime of cells (Strehler, 1966; Novelli, 1970; Hayflick, 1965, 1974), crosslinking of macromolecules (Bjorksten, 1968), somatic mutation (Mole, 1963; Jones and Kimmeldorf, 1964), accumulation of random errors (Orgel, 1963, 1973), dietary caloric intake (Ross, 1959; Mclntyre et al., 1964), and many others.


Life Span Dizygotic Twin Bronchogenic Carcinoma Evolutionary Aspect Dwarf Mouse 
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  1. Adelman, R. C., Stein, G., Roth, G. S., and Englander, D., 1972, Age-dependent regulation of mammalian DNA synthesis and cell proliferation in vivo, in: Mechanisms of Ageing and Development, Vol. 1, pp. 49–59, Elsevier Sequoia S.A., The Netherlands.Google Scholar
  2. Altman, P. L., and Dittmer, D. S., 1972, Biology Data Book, Vol. I, Federation of American Societies for Experimental Biology, Bethesda, Maryland.Google Scholar
  3. Baker, P. J., Stasliak, P. W., Amsbaugh, D. F., and Prescott, B., 1974, Regulation of the antibody response to type III pneumococcal polysaccharide. III. Mode of action of thymic-derived suppressor cells, J. Immunol. 1120:404–409.Google Scholar
  4. Bellamy, D., 1967, Hormonal effects in relation to ageing in mammals, Symp. Soc. Exp. Biol. 21:427–450.PubMedGoogle Scholar
  5. Benacerraf, B., and McDevitt, H. O., 1972, Histocompatibility-linked immune response-genes; a new class of genes that controls the formation of specific tissue responses has been identified, Science 175:273–279.PubMedCrossRefGoogle Scholar
  6. Bjorksten, J., 1968, The crosslinkage theory of aging, J. Am. Geriat. Soc. 16:408–427.PubMedGoogle Scholar
  7. Buerger, M., 1957, Biomorphose oder Gerontologie?, Z. Altersforsch 10:279–283.Google Scholar
  8. Burnet, F. M., 1973, A genetic interpretation of ageing, Lancet 2:480–483.PubMedCrossRefGoogle Scholar
  9. Childs, B., 1975, Prospects for genetic screening, J. Pediat. 87:1125–1132.PubMedCrossRefGoogle Scholar
  10. Childs, B., and Der Kaloustian, V. M., 1968, Genetic heterogeneity, New Engl. J. Med. 279:1205–1212, 1267–1274.PubMedCrossRefGoogle Scholar
  11. Comfort, A., 1974, The position of aging studies, in: Mechanisms of Aging and Development, Vol. 3, pp. 1–31, Elsevier Sequoia S.A., Lausanne, The Netherlands.Google Scholar
  12. Cooper, D. M., Hoeppner, V., Cox, D., Zamel, N., Bryan, A. C., and Levison, H., 1974, Lung function of alpha1-antitrypsin heterozygotes (Pi type MZ), Am. Rev. Resp. Dis. 110:708–715.PubMedGoogle Scholar
  13. Danowski, T. S., Tsai, C. T., Morgan, C-R., Sieracki, J. C., Alley, R. A., Robbins, T. J., Sabeh, G., and Sunder, J. H., 1969, Serum growth hormone and insulin in females without glucose intolerance, Metabolism 18:811–820.PubMedCrossRefGoogle Scholar
  14. Dilman, V., 1971, Age associated elevation of hypothalamic threshhold to feedback control and its role in development, ageing, and disease, Lancet 1:1211–1219.PubMedCrossRefGoogle Scholar
  15. Doherty, P. C., and Zinkernagel, R. M., 1975, A biological role for the major histocompatibility antigens, Lancet 1:1406–1409.PubMedCrossRefGoogle Scholar
  16. Dorf, M., Balner, H., and Benacerraf, B., 1975a, Mapping of the immune response genes in the major histocompatibility complex of the Rhesus monkey, J. Exp. Med. 142:673–693.PubMedCrossRefGoogle Scholar
  17. Dorf, M., Stimpfling, J., and Benacerraf, B., 1975b, Requirement for two H-2 complex Ir genes for the immune response to the L-GLU, L-LYS, L-PHE Ter polymer, J. Exp. Med. 141:1459–1463.Google Scholar
  18. Duquesnoy, R., 1975, The pituitary dwarf mouse: A model for study of indocrine immunodeficiency disease, in: Immunodeficiency in Man and Animals (D. Bergsma, R. A. Good, and J. Finstad, eds.), Birth Defects Original Series, 21(1):536–543.Google Scholar
  19. Fabris, N., 1975, Relation of lymphoid system and hormones to aging, in: Immunodeficiency in Man and Animals (D. Bergsma, R. A. Good, and J. Finstad, eds.), Birth Defects Original Series 21(1):533–535.Google Scholar
  20. Frelinger, J. A., Niederhuber, J. E., and Schreffler, D. C., 1975, Inhibition of immune responses in vitro by specific antiserums to Ia antigens, Science 188:268–270.PubMedCrossRefGoogle Scholar
  21. Friedenthal, H., 1910, Über die Gultigkeit der Massenwirkung für den Energiemsatz der lebendigen Substanz, Zentralbl. Physiol. 24:321–337.Google Scholar
  22. Garcia, M. J., McNamara, P. M., Gordon, T., and Kanneil, W. B., 1974, Morbidity and mortality in diabetics in the Framingham population. Sixteen year follow-up study, Diabetes 23:105–116.PubMedGoogle Scholar
  23. Gelfant, S., and Grove, G. L., 1974, Cycling ⇄ noncycling cells as an explanation for the aging process, in: Symp. on the Theoretical Aspects of Aging (M. Rockstein, ed.), pp. 105–177, Academic Press, New York, San Francisco, London.Google Scholar
  24. Gershon, R. K., and Hencin, R. S., 1971, The DNA synthetic response of adoptively transferred thymocytes in the spleens of lethally irradiated mice, J. Immunol. 197:1723–1728.Google Scholar
  25. Gershon, R. K., and Liebhaber, S. A., 1972, The response of T cells to histocompatibility-2 antigens, dose-response kinetics, J. Exp. Med. 136:112–127.PubMedCrossRefGoogle Scholar
  26. Gertler, M. M., and White, P. D., 1954, Coronary Heart Disease in Young Adults; A Multidisciplinary Study, Harvard University Press, Cambridge, Massachusetts.Google Scholar
  27. Goldstein, J. L., 1973, Genetic aspects of hyperlipidemia in coronary heart disease, Hosp. Practice (October):53–65.Google Scholar
  28. Goldstein, S., 1971a, The biology of aging, New Engl. J. Med. 285:1120–1129.PubMedCrossRefGoogle Scholar
  29. Goldstein, S., 1971b, Analytical review: The pathogenesis of diabetes mellitus and its relationship to aging, Humangenetik 12:83–100.PubMedCrossRefGoogle Scholar
  30. Gottlieb, M. S., and Root, H. F., 1968, Diabetes mellitus in twins, Diabetes 17:693–704.PubMedGoogle Scholar
  31. Greenberg, L. J., and Yunis, E. J., 1972, Immunologic control of aging: A possible primary event, Gerontologia 18:247–266.PubMedCrossRefGoogle Scholar
  32. Greenberg, L. J., and Yunis, E. J., 1975, Immunogenetic aspects of viral oncogenesis, in: Molecular Pathology (R. A. Good, S. Day, and J. J. Yunis, eds.), pp. 328–353, Charles C Thomas, Springfield, Illinois.Google Scholar
  33. Harris, H., 1950, The familial distribution of diabetes mellitus: A study of the relatives of diabetic propositi, Ann. Eugen. (London) 15:95–119.CrossRefGoogle Scholar
  34. Harris, H., and Hopkinson, D. A., 1972, Average heterozygosity per locus in man; an estimate based on the incidence of enzyme polymorphisms, Ann. Hum. Genet. 36:9–20.PubMedCrossRefGoogle Scholar
  35. Harvald, B., and Hauge, M., 1970, Coronary occlusion in twins, Acta Geneticae Medicae et Gemellologiae 19:248–250.PubMedGoogle Scholar
  36. Hawkins, M. R., Murphy, E. A., and Abbey, H., 1965, The familial component in longevity. A study of the offspring of nonagenarians. I. Methods and preliminary report, Bulletin of the Johns Hopkins Hospital 117:24–36.PubMedGoogle Scholar
  37. Hayflick, L., 1965, The limited in vitro lifetime of human diploid cell strains, Exp. Cell Res. 37:614–636.PubMedCrossRefGoogle Scholar
  38. Hayflick, L., 1974, The longevity of cultured human cells, Am. Geriatrics Soc. 22:1–12.Google Scholar
  39. Heidrick, M. L., and Makinodan, T., 1972, Nature of cellular deficiencies in age-related decline of the immune system, Gerontologia 18:305–320.PubMedCrossRefGoogle Scholar
  40. Hoffman, M., and Kappler, J. W., 1972, The antigen specificity of thymus derived helper cells, J. Immunol. 108:261–263.Google Scholar
  41. Hori, Y., Perkins, E. H., and Halsall, M. K., 1973, Decline of phytohemagglutinin responsiveness of spleen cells from aging mice (37524), Proc. Soc. Exp. Biol. Med. 144:48–53.PubMedGoogle Scholar
  42. Jones, D. C. L., and Kimmeldorf, D. J., 1964, Effect of age at irradiation on life span in the male rat, Radiai. Res. 22:106–115.CrossRefGoogle Scholar
  43. Kallman, F. J., and Jarvik, L., 1959, Individual differences in constitution and genetic background, in: Handbook of Aging and the Individual; Psychological and Biological Aspects (J. E. Birren, ed.), pp. 216–263, University of Chicago Press, Chicago, Illinois.Google Scholar
  44. Kallman, F. J., and Sander, G., 1948, Twin studies on aging and longevity, J. Heredity 39:349–357.Google Scholar
  45. Kellerman, G., Luyten-Kellerman, M., and Shaw, C. R., 1973a, Genetic variation of aryl hydrocarbon hydroxylase in human lymphocytes, Am. J. Hum. Genet. 25:327–331.Google Scholar
  46. Kellerman, G., Shaw, C. R., and Luyten-Kellerman, M., 1973b, Aryl hydrocarbon hydroxylase induci-bility and bronchogenic carcinoma, New Engl. J. Med. 289:934–937.CrossRefGoogle Scholar
  47. Landahl, H. D., 1959, in: Handbook of Aging and the Individual; Psychological and Biological Aspects (J. E. Birren, ed.), pp. 81–118, University of Chicago Press, Chicago, Illinois.Google Scholar
  48. Lansing, A. I., 1959, General biology of senescence, in: Handbook of Aging and the Individual; Psychological and Biological Aspects (J. E. Birren, ed.), pp. 119–135, University of Chicago Press, Chicago, Illinois.Google Scholar
  49. Lilly, F. J., 1968, The effect of histocompatibility-2 type on response to the Friend leukemia virus in mice, J. Exp. Med. 127:465–473.PubMedCrossRefGoogle Scholar
  50. Lilly, F. J., 1971, The influence of H-2 type on gross virus leukemogenesis in mice, Transplant. Proc. 3:1239–1242.Google Scholar
  51. McDevitt, H. O., and Benacerraf, B., 1969, Genetic control of specific immune responses, Adv. Immunol. 11:31–74.PubMedCrossRefGoogle Scholar
  52. McDevitt, H. O., and Bodmer, W. F., 1974, HL-A immune-response genes and disease, Lancet 1:1269–1275.PubMedCrossRefGoogle Scholar
  53. Mclntyre, K. R., Sell, S., and Miller, J. F. A. P., 1964, Pathogenesis of the post-neonatal thymectomy syndrome, Nature (London) 204:151–155.CrossRefGoogle Scholar
  54. Michael, A. F., Drummond, K. N., Good, R. A., and Vernier, R. L., 1966, Acute poststreptococcal glomerulonephritis: Immune deposit disease, J. Clin. Invest. 45:237–248.PubMedCrossRefGoogle Scholar
  55. Miller, J. H., and Shock, N. W., 1953, Age differences in the renal tubular response to antidiuretic hormone, J. Gerontol. 8:446–450.PubMedGoogle Scholar
  56. Mole, R. H., 1963, in: Cellular Basis and Aetiology of Late Somatic Effects of Ionizing Radiation (H. Harris, ed.), pp. 273–276, Academic Press, New York.Google Scholar
  57. Neel, J. V., Fajans, S. S., Conn, J. W., and Davidson, R. T., 1965, Symposium diabetes mellitus, in: Genetics and the Epidermiology of Chronic Diseases (J. V. Neel, M. W. Shaw, and W. J. Schull, eds.), pp. 105–132, Public Health Service Publication #1163.Google Scholar
  58. Novelli, G. D., 1970, Regulation at the cellular level, with possible reference to differentiation and possible mechanisms of aging, in: Symposium on Cellular and Macromolecular Aspects of Aging, Oak Ridge Nat. Lab., Gatlinburg.Google Scholar
  59. Orgel, L. E., 1963, The maintenance and accuracy of protein synthesis and its relevance to ageing, Proc. Nat. Acad. Sci. U.S.A. 49:517–521.PubMedCrossRefGoogle Scholar
  60. Orgel, L. E., 1973, Ageing of clones of mammalian cells, Nature 243:441–445.PubMedCrossRefGoogle Scholar
  61. Ostrander, L. D., Lamphiear, D. E., Block, W. D., Johnson, B. C., and Epstein, F. H., 1974, Biochemical precursors of atherosclerosis, Arch. Intern. Med. 134:224–230.PubMedCrossRefGoogle Scholar
  62. Post, J., and Hoffman, J., 1968, Cell renewal patterns, New Engl. J. Med. 279:248–258.PubMedCrossRefGoogle Scholar
  63. Price, G. B., and Makinodan, T., 1972, Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies, J. Immunol. 108:403–412.PubMedGoogle Scholar
  64. Ram, J. S., 1967, Aging and immunological phenomena. A review, J. Gerontol. 22:92–107.PubMedGoogle Scholar
  65. Rich, R. R., and Pierce, C. W., 1975, Biological expressions of lymphocyte activation. II. Generation of a population of thymus derived suppressor lymphocytes, J. Exp. Med. 137:649–659.CrossRefGoogle Scholar
  66. Rimoin, D.L., 1967, Genetics of diabetes mellitus, Diabetes 16:346–351.PubMedGoogle Scholar
  67. Roberts-Thomson, I. C., Whittingham, S., Youngchaiyud, U., and MacKay, I. R., 1974, Ageing, immune response, and mortality, Lancet 2:368–370.PubMedCrossRefGoogle Scholar
  68. Rose, G., 1964, Familial patterns in ischaemic heart disease, Brit. J. of Preventive and Social Medicine 18:75–80.Google Scholar
  69. Rosenbloom, A. L., 1970, Insulin responses of children with chemical diabetes mellitus, New Engl. J. Med. 282:1228–1231.PubMedCrossRefGoogle Scholar
  70. Ross, M. H., 1959, Proteins, calories and life expectancy, Fed. Proc. 18:1190–1207.PubMedGoogle Scholar
  71. Rubner, M., 1908a, Problemes des Wachstums und der Lebensdauer, Gesellschaft fur innere Medizin und Kinderheilkunde, Wien, Mitteilungen, Beiblatt, Vol. 7, 58–81.Google Scholar
  72. Rubner, M., 1908b, Das Problem der Lebensdauer und seine Beziehungen zum Wachstum and Ernahrung, Oldenbourg, Munich.Google Scholar
  73. Ryder, L. P., Staub-Nielsen, L., and Svejgaard, A., 1974, Association between HLA histocompatibility antigens and non-malignant diseases, Humangenetik 25:251–264.PubMedCrossRefGoogle Scholar
  74. Sacher, G. A., 1975, Maturation and longevity in relation to the cranial capacity in hominid evolution, in: Antecedents of Man and After. I. Primates: Functional morphology and evolution (R. Tuttle, ed.), pp. 417–441, Mouton Publishers, The Hague.Google Scholar
  75. Sacher, G. A., 1976, Evaluation of the entropy and information terms governing mammalian longevity, in: Interdisciplinary Topics of Gerontology (R. G. Cutler, ed.), Vol. 9, pp. 69–82, Karger, Basel.Google Scholar
  76. Sacher, G. A., and Staffeidt, E. F., 1974, Relationship of gestation time to brain weight for placental mammals: Implications for the theory of vertebrate growth, The Am. Naturalist 108:593–615.CrossRefGoogle Scholar
  77. Scriver, C. R., Neal, J. L., Saginur, R., and Clow, A., 1973, The frequency of genetic disease and congenital malformation among patients in a pediatric hospital, Can. Med. Assoc. J. 108:1111–1115.PubMedGoogle Scholar
  78. Shock, N. W., 1974, Physiological theories of aging, in: Theoretical Aspects of Aging, (M. Rockstein, ed.), pp. 119–136, Academic Press, New York, San Francisco, London.Google Scholar
  79. Shock, N. W., and Andres, R., 1968, in: Adaptive Capacities of an Aging Organism (D. F. Chebatarev, ed.), pp. 235–254, Acad. Sci. USSR, Kiev.Google Scholar
  80. Shreffler, D. C., and David, C. S., 1975, The H-2 major histocompatibility complex and the I immune response region: Genetic variation, function, and organization, in: Advances in Immunology (W. H. Taliaferro and J. H. Humphrey, eds.), Vol. 20, p. 125, Academic Press, New York.CrossRefGoogle Scholar
  81. Silverstone, F. A., Bradfonbrener, M., Shock, N. W., and Yiengst, M. J., 1957, Age differences in the intravenous glucose tolerance test and the response to insulin, J. Clin. Invest. 36:504–514.PubMedCrossRefGoogle Scholar
  82. Simpson, N. E., 1962, The genetics of diabetes: A study of 233 families of juvenile diabetics, Ann. Hum. Genet. 26:1–21.PubMedCrossRefGoogle Scholar
  83. Slack, J., 1974, Genetic differences in liability to atherosclerotic heart disease, J. Roy. Coll. Phycns. Lond. 8:115–126.Google Scholar
  84. Slack, J., and Evans, K. A., 1966, The increased risk of death from ischaemic heart disease in first degree relatives of 121 men and 96 women with ischaemic heart disease, J. Med. Genet. 3:239–257.PubMedCrossRefGoogle Scholar
  85. Strehler, B., 1966, Code degeneracy and the aging process. A molecular-genetic theory of aging, Proc. 7th Int. Congr. of Gerontology 1:177–185.Google Scholar
  86. Svejgaard, A., Platz, P., Ryder, L. P., Staub-Nielsen, L., and Thomsen, M., 1975, HLA and disease associations—A survey, Transplant Rev. 22:3–43.PubMedGoogle Scholar
  87. Talamo, R. C., 1975, Basic and clinical aspects of the alpharantitrypsin, Pediat. 56:91–99.Google Scholar
  88. Tattersall, R. B., 1974, Mild familial diabetes with dominant inheritance, Quart. J. Med. 43:339–357.PubMedGoogle Scholar
  89. Vladutiu, A. O., and Rose, N. R., 1971, Autoimmune murine thyroiditis: Relations to histocompatibility (H-2) type, Science 174:1137–1139.PubMedCrossRefGoogle Scholar
  90. Walford, R. L., 1969, The Immunologic Theory of Aging, Munksgaard, Copenhagen.Google Scholar
  91. Walford, R. L., 1970, Antibody diversity, histocompatibility systems, disease states, and aging, Lancet 2:1226–1229.PubMedCrossRefGoogle Scholar
  92. Walford, R. L., 1974, Immunologic theory of aging: Current status, Fed. Proc. 33:2020–2027.PubMedGoogle Scholar
  93. Yunis, E. J., Fernandes, G., and Greenberg, L. J., 1975, Deficiency, autoimmunity and aging, Birth Defects Original Series 11:185–192.Google Scholar
  94. Yunis, E. J., and Greenberg, L. J., 1974, Immunopathology of aging, Fed. Proc. 33:2017–2019.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1977

Authors and Affiliations

  • Jorge J. Yunis
    • 1
  • Leonard J. Greenberg
    • 1
  • Edmond J. Yunis
    • 1
  1. 1.Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA

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