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.