Mutation and senescence: where genetics and demography meet.

Two evolutionary genetic models-mutation accumulation and antagonistic pleiotropy-have been proposed to explain the origin and maintenance of senescence. In this paper, we focus our attention on the mutation accumulation model. We re-examine previous evidence for mutation accumulation in light of new information from large-scale demographic experiments. After discussing evidence for the predictions that have been put forth from models of mutation accumulation, we discuss two critical issues at length. First, we discuss the possibility that classical fruit fly stock maintenance regimes may give rise to spurious results in selection studies of aging. Second, we consider evidence for the assumptions underlying evolutionary models of aging. These models assume that mutations act additively on age-specific survival rate, that there exist mutations whose effects are confined to late age-classes, and that all mutations have equal effects. Recent empirical evidence suggests that each of these three assumptions is unlikely to be true. On the basis of these results, we do not conclude that mutation accumulation is no longer a valid explanation for the evolution of aging. Rather, we suggest that we now need to begin developing more biologically realistic genetic models for the evolution of aging.