[
1996]
Species with short life spans have been the primary targets for studies into the genetic basis of the aging process(es). Almost all genetic studies of aging and longevity have been performed on invertebrates. Invertebrates often have very short life spans, and this fact, together with the excellent genetic systems available for some yeasts, Drosophila melanogaster, and the nematode Caenorhabditis elegans, make them almost the only choice for studying the genetics of aging. The mouse, with its 2-year life span, is an exception to this rule; several genetic studies, including the analysis of short-lived mice, have been performed and used in an attempt to infer causal relationships. The mouse is the focus of a recent NIA initiative on mammalian models of aging. Recently human marker association" studies, where longevity is shown to be associated with defined regions of the human genome by characterizing molecular markers at certain candidate loci, have started to appear. Genetic approaches have been used also to identify the processes causing replicative senescence in human tissue culture. Two fundamentally distinct but overlapping questions have been the focus of genetic studies. What are the molecular mechanisms limiting life span? How does the process of evolution lead to aging and senescence? Although the answer to the latter question has been obtained to the satisfaction of most in the field, studies into the molecular basis continue. The details of the mechanisms leading to senescence and aging have not been forthcoming. Genetic approaches promise to fill this gap.