GENETICS OF AGING - CURRENT ANIMAL-MODELS

Studies are summarized for three organisms-Caenorhabditis elegans, Mus musculus, and Drosophila melanogaster-utilizing three distinct approa ches to the identification of longevity-determining genes: the analysi s of mutations that affect life span, the use of transgenic animals to assess the effects of specific gene expression on longevity, and sele ctive breeding to identify naturally occurring allelic variations betw een strains that have differential effects on life span. Correlative s tudies of age-dependent changes in physiology, or in cellular and mole cular constituents, generally cannot discern cause from effect. In con trast, analyses of genetic influences on longevity can permit underlyi ng mechanisms to be reliably inferred; because genotype remains essent ially constant throughout life, longevity comparisons of animals diffe ring 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 deteriorat ion and disease.