Sex- and age-dependent genetics of longevity in a heterogeneous mouse population

DNA variants that modulate lifespan provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (QTL) on chromosome 12 and identified sex-specific QTLs, some of which detected only in older mice. Similar relations between life history and longevity were uncovered in mice and humans, underscoring the importance of early access to nutrients and early growth. We identified common, age- and sex-specific genetic effects on gene expression that we integrated with model organism and human data to create a hypothesis-building interactive resource of prioritized longevity and body weight genes. Finally, we validated Hipk1, Ddost, Hspg2, Fgd6, and Pdk1 as conserved longevity genes using C. elegans lifespan experiments. RNA sequencing of livers of male and female UM-HET3 mice at two ages, 6 months and 22 months.