Analysis of lifespan across diversity outbred mouse studies identifies multiple longevity-associated loci
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.
Authors
- Kevin Flurkey
- Andrea Di Francesco (ORCID: https://orcid.org/0000-0001-6867-8203)
- Jonathan R. Archer
- Gary A. Churchill (ORCID: https://orcid.org/0000-0001-9190-9284)
- Kevin M. Wright (ORCID: https://orcid.org/0000-0001-8772-2687)
- Anil Raj (ORCID: https://orcid.org/0000-0003-4412-0883)
- Martin N. Mullis (ORCID: https://orcid.org/0000-0002-5134-7528)
- Daniel M. Gatti (ORCID: https://orcid.org/0000-0003-0667-9926)
- J. Graham Ruby (ORCID: https://orcid.org/0000-0002-4798-5420)
- Ron Korstanje (ORCID: https://orcid.org/0000-0002-2808-1610)
- Peter C. Reifsnyder (ORCID: https://orcid.org/0000-0001-5666-8040)
- David E. Harrison
- Karen L. Svenson (ORCID: https://orcid.org/0000-0002-7928-1911)
- Laura Robinson
Institutions
- Enzo Life Sciences (United States) (US)
- Jackson Laboratory (US)
Publication Details
- Journal
- Genetics
- Published
- 2025-05-06
- DOI
- https://doi.org/10.1093/genetics/iyaf081
- Citations
- 3
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 2.86
Funders
- Ellison Medical Foundation
- National Institutes of Health