Traits that influence longevity in mice: a second look

Analysis of genetic interactions in the F2 of an intercross of (C57BL/6 x DBA/2) F1J revealed influences of genetic factors on life span. Females lived longer than males. Dilute brown females died sooner than females of other colors. H-2b/H-2b males died sooner than H-2b/H-2d or H-2d/H-2d males, except that among dilute brown males those of typeH-2b/H-2d died sooner. Cluster analysis suggested that male and female genotypes each fall into two groups, with female dilute brown mice having shorter lives than other females, and male H-2b/H-2b mice except dilute brown and dilute brown H-2b/H-2d mice having shorter lives than other males. The association of heterozygosity with life span was clearer in females than in males, yet the longest-lived female genotype was homozygous H-2d/H-2d, of dominant Black phenotype at the Brown locus of chromosome 4, and homozygous dd at the Dilute locus of chromosome 9. The shortest-lived females were dilute brown H-2b/H-2b. The longest-lived and shortest-lived male genotypes were dilute brown H-2d/H-2d and dilute brown H-2b/H-2d, respectively. Although histological findings at postmortem differed between the sexes, there was no association of particular disorders with other genetic markers. The importance of H-2 in males was confirmed, but the allelic effects were perturbed, possibly by the absence of Sendai infection in this experiment. Overall our studies suggest that genetic influences on life span involve interactions between loci, and allelic interactions may change with viral infections or other environmental factors.