Analysis of lifespan across Diversity Outbred mouse studies identifies multiple longevity-associated loci

Mullis, M. N., Wright, K. M., Raj, A., Gatti, D. M., Reifsnyder, P., Flurkey, K., Archer, J. R., Robinson, L., Di Franscesco, A., Svenson, K. L., Korstanje, R., Harrison, D. E., Ruby, J. G., Churchill, G. A.

The Jackson Laboratory · biorxiv

Paper

Abstract

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conduct a genetic meta-analysis of longevity in Diversity Outbred (DO) mice that includes 2,444 animals from three independently conducted lifespan studies. We identify six loci that contribute significantly to lifespan independently of diet and drug treatment, one of which also influences lifespan in a sex-dependent manner, as well as an additional locus with a diet-specific effect on lifespan. Collectively, these loci explain over half of the estimated heritable variation in lifespan across these studies and provide insight into the genetic architecture of lifespan in DO mice.

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Research summary

The paper is relevant to longevity research as it investigates the genetic factors associated with lifespan in mice, contributing to our understanding of the genetic architecture of aging. The identification of multiple loci that influence lifespan independently of external factors is significant, as it provides insights into the biological mechanisms underlying longevity. However, while the findings are important, they are based on a specific model organism and may not directly translate to human aging, limiting their broader impact on the field.

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