Heritability of life span in mice and its implication for direct and indirect selection for longevity

We found high narrow-sense heritability of life span based on the regressio n of offspring on average parental (midparent) life spans. In two mouse pop ulations prepared using the 4-way-cross design, mean +/- SE heritabilities were 62 +/- 11% (P less than or equal to 0.001) and 44 +/- 15% (P less than or equal to 0.01). To reflect inherited rates of aging, rather than resist ance to early disease, data from the first 25% to die were deleted, so that only about 40% of families were used for offspring-midparent regressions. Heritabilities still remained high, 38% and 55%, for the same two populatio ns, respectively. Populations studied in two other experiments did not show nearly as high heritabilities; in one case probably due to environmental s tress, and in the other probably because the strains used did not have suff icient additive variance in genes regulating longevity. Significant heritab ilities occurred only when a wild derived inbred strain was included in the 4-way cross. The age when a female ceased to reproduce appeared to be rela ted to the life spans of her offspring, but only weakly, not approaching si gnificance for any individual experiment. The age when a female became infe rtile was related to her life span, but the relationship disappeared when s hort-lived mice were excluded from the analysis. Our findings indicate that , in sufficiently diverse mouse populations, selection for increased longev ity should be possible and that the direct selection for parental life span will be a more efficient strategy than selection for female reproductive l ife span.