Large-scale mouse study finds sex- and age-dependent genetic effects on longevity

In a new study of more than 3,000 genetically diverse mice in a multicenter, multiyear project on healthy aging, Maroun Bou Sleiman and colleagues identified several genetic loci that correlate with longevity, offering a new glimpse at how DNA variants can impact the lifespan. The researchers show that the contribution of various genes to longevity varies between males and females, and that some genes do not affect lifespan until the mice – in particular, male mice – reach a certain age. Several of these genetic loci were also correlated with longevity in humans and in the worm C. elegans, suggesting that they have been evolutionarily conserved. Bou Sleiman et al. found some overlap between longevity loci and loci correlated to body weight and growth, confirming that longevity is likely the result of a complex interaction between multiple traits. The researchers note that early-life nutrition in the mice also had a significant impact on longevity, as it does in humans. In a related Perspective, João Pedro de Magalhães writes that the heterogeneous makeup of the mouse study population was important in uncovering these sex-specific effects in longevity, and underscores "the need to study diverse populations in longevity and other complex diseases and traits."