Somatic mutagenesis and antimutagenesis in aging research.
Somatic mutagenesis and antimutagenesis are reviewed from the point of view of a gerontologist. Aging can be defined as a set of phenotypes that have escaped the force of natural selection. In mammalian species, aberrations in proliferative homeostasis, including a variety of cancers, are conspicuous examples. The author argues that there is a strong coupling between intrinsic biological aging and the biology of neoplasia. Genomic instability is likely to be a dominant mechanism underlying such coupling. Ongoing experiments from his laboratory and those of collaborators are briefly reviewed. The approaches include: (1) the characterization of a striking progeroid mutation of man, the Werner syndrome, which exhibits a deletor mutator phenotype; (2) the comparative analysis of intragenic and chromosomal mutations in mammalian species of contrasting life span potentials; (3) attempts to synthesize antimutator strains of mice. An emerging generalization is that there is a significant degree of species specificity in the patterns of somatic mutation in aging mammals.
Martin
G M
GM
Department of Pathology, University of Washington, Seattle 98195, USA.
D000375:Aging / Q000235:genetics*; D000818:Animals; D005075:Biological Evolution; D006801:Humans; D008136:Longevity / Q000235:genetics; D051379:Mice; D016296:Mutagenesis / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics; D018384:Oxidative Stress; D011371:Progeria / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism