All sexually reproducing species, in their genomes, carry numerous allelic variants predisposing to slow senescence and extended longevity (vitality). All also include numerous variants predisposing to more rapid senescence and shorter life (frailty). Still, the majority of our available alleles are likely to have little direct influence on life span. In wild populations, senescence-promoting (frailty) and senescence-slowing (vitality) variants are likely to be in balance. Alleles predisposing to senescence slowing, and those that shorten life too greatly (high fraility), generally are outcompeted by those predisposing to more modal life spans and reproductive success. Over evolutionary time, genetic variants promoting longevity and nongevity likely have, for most wild populations, been “non-essential” with respect to natural selection and reproductive success (RS). Allelic frequencies for such variants will drift along randomly, except when very early senescence-promoting types reduce RS sufficiently to be selected against. Life extension experiments on laboratory models (calorie restriction, late reproduction, temperature modulation, selective breeding, and transgenic manipulation) expose this underlying DNA variation. In some cases, by revealing genetically determined phenotypic plasticity in response to harsh environments, in others, by selecting more long-lived phenotypes with underlying alleles predisposing carriers to late-life reproduction and survival (traits not conducive to high RS in the wild) to produce later generations. Similarly, reports showing longevity-enhancing or -retarding DNA/protein variants with increased/decreased expression of specific proteins (superoxide dismutasel (SOD), catalase, and the like) and linkage of allelic variants at specific loci to life extension reveal simple mechanisms with large influences on rodent, insect, and worm life spans.