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Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci

2025/05/06 by Martin N. Mullis, Kevin M. Wright, Anil Raj +11 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Genetics, Aging, and Longevity in Model Organisms #Adipose Tissue and Metabolism #Genetic Mapping and Diversity in Plants and Animals

paper · pdf · doi:10.1093/genetics/iyaf081

openalex publication_date 2025/05/06 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31

Abstract

Lifespan is an integrative phenotype whose genetic architecture is likely to highlight multiple processes with high impact on health and aging. Here, we conducted a genetic mega-analysis of longevity in Diversity Outbred (DO) mice that included 2,444 animals from 3 independently conducted lifespan studies. We identified 8 loci that contributed significantly to lifespan independently of diet and drug treatment in at least one study. One of these loci also influenced lifespan in a sex-dependent manner, and we detected an additional locus with a diet-specific effect on lifespan. Collectively, these loci explained over half of the estimated heritable variation in lifespan across these studies and provided insight into the genetic architecture of lifespan in DO mice.

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