Genetic and evolutionary aspects of aging.
Four questions of fundamental importance to gerontology are considered. 1) The number of genes involved in aging--in the case of man, an analysis of the phenotypes of relevant spontaneous mutants indicates that aging is highly polygenic. 2) General categories of genes--regulator genes may be more relevant than structural genes: a) three aneuploid disorders, Down's, Turner's and Klinefelter's syndromes, ranked among the top 10 candidates as "segmental progeroid syndromes" when compared with 162 single gene disorders of relevance to the pathobiology of aging; b) the rates at which maximum life spans have been increasing, especially among hominids, have probably been too rapid to be accounted for by changes in the amino acid sequences of proteins; c) a preliminary analysis of the variance of maximum life spans among a few orders of mammals is suggestive of a linear correlation with the indexes of rates of chromosomal evolution, as estimated by Bush et al. (Proc. Natl. Acad. Sci. USA 74: 3942-3946, 1977). 3) Nature of gene action--although there are reasons for invoking genes that modulate the rates of accumulation of somatic mutations, differential regulation of development is likely to be a major setting for gene action. 4) New approaches to formal genetic analysis of aging--advances in experimental embryology and somatic cell genetics offer such opportunities.
D000368:Aged; D000375:Aging; D000818:Animals; D005075:Biological Evolution; D002874:Chromosome Mapping; D004314:Down Syndrome / Q000503:physiopathology; D005260:Female; D005796:Genes; D005809:Genes, Regulator; D006801:Humans; D007713:Klinefelter Syndrome / Q000503:physiopathology; D008136:Longevity; D008297:Male; D009369:Neoplasms / Q000503:physiopathology; D014424:Turner Syndrome / Q000503:physiopathology