Genetics of aging: current animal models

Studies are summarized for three organisms-Caenorhabditis elegans, Mus musculus, and Drosophila melanogaster-utilizing three distinct approaches to the identification of longevity-determining genes: the analysis of mutations that affect life span, the use of transgenic animals to assess the effects of specific gene expression on longevity, and selective breeding to identify naturally occurring allelic variations between strains that have differential effects on life span. Correlative studies of age-dependent changes in physiology, or in cellular and molecular constituents, generally cannot discern cause from effect. In contrast, analyses of genetic influences on longevity can permit underlying mechanisms to be reliably inferred; because genotype remains essentially constant throughout life, longevity comparisons of animals differing only in genetic constitution must reflect the effects of genes on long-term survival. Understanding the genetic regulation of life span may thus lead to methods of intervention in age-associated deterioration and disease.