Maximum life spans in mice are extended by wild strain alleles

The genes that control basic aging mechanisms in mammals are unknown. By using two four-way crosses, each including a strain derived from wild, undomesticated stocks, we identified two quantitative trait loci that extend murine life spans by approximately 10%. In one cross, the longest-lived 18% of carriers of the D8Mit171 marker allele from the MOLD/Rk strain, Mus m. molossinus, outlived the longest lived 18% of noncarriers by 129 days (P = 5.4 x 10(-5)); in a second cross, carriers of the D10Mit267 allele from the CAST/Ei strain, Mus m. castaneus, outlived noncarriers by 125 days (P = 1.6 x 10(-6)). In both crosses, P < 1.0 x 10(-4) is considered significant. Because these life span increases required that all essential biological systems function longer than normal, these alleles most likely retarded basic aging mechanisms in multiple biological systems simultaneously.