Document Type
Article
Publication Date
8-6-2025
Original Citation
Mullis M,
Wright K,
Raj A,
Gatti D,
Reifsnyder PC,
Flurkey K,
Archer J,
Robinson L,
Di Francesco A,
Svenson KL,
Korstanje R,
Harrison D,
Ruby J,
Churchill G.
Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci. Genetics. 2025;230(4):iyaf081.
Keywords
JMG, Animals, Longevity, Mice, Male, Quantitative Trait Loci, Female, Animals, Outbred Strains
JAX Source
Genetics. 2025;230(4):iyaf081.
ISSN
1943-2631
PMID
40326784
DOI
https://doi.org/10.1093/genetics/iyaf081
Grant
This work was funded by National Institutes of Health grants AG038070, AG022308, and AG079753, the Ellison Medical Foundation (G.A.C.), and by Calico Life Sciences LLC
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.