Sex- and age-dependent genetics of longevity in a heterogeneous mouse population
- 1. Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne; Lausanne 1015, Switzerland
- 2. Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center (UTHSC); Memphis, TN, USA.
- 3. Institute of Primary Care and Public Health (Unisante), University of Lausanne; Lausanne, Switzerland. Swiss Institute of Bioinformatics; Lausanne, Switzerland. Department of Computational Biology, University of Lausanne; Lausanne, Switzerland.
- 4. Department of Preventive Medicine, University of Tennessee Health Science Center; Memphis, TN, USA.
- 5. The Jackson Laboratory; Bar Harbor, ME 04609, USA.
- 6. Barshop Center for Longevity Studies at the University of Texas Health Science Center at San Antonio; San Antonio 78229 USA.
- 7. Department of Pathology, University of Michigan Geriatrics Center; Ann Arbor, MI, USA
Description
Follow this hyperlink to the interactive application that supports the publication "Sex- and age-dependent genetics of longevity in a heterogeneous mouse population" with the DOI: 10.1126/science.abo3191.
DNA variants that modulate lifespan are beginning to provide a systematic and unbiased insight into determinants of health, disease and aging. Through genetic analyses in the large UM-HET3 F2 intercross used by the NIA Interventions Testing Program (ITP), we detect a known sex-independent quantitative trait locus (QTL) on chromosome 12 and identify novel and known sex-specific QTLs, some of which become detectable only in older mice. Similar relations between life history traits and longevity were uncovered in both mice and humans, underscoring the importance of early access to nutrients and early growth on longevity. Gene expression analysis identified common, age- and sex-specific genetic effects on gene expression. Through orthogonal model organism and human data integration, we provide candidate longevity genes and prioritize using C. elegans lifespan experiments Hipk1, Ddost, Hspg2, Fgd6, and Pdk1 as promising and conserved longevity genes. Finally, we provide an interactive hypothesis-building resource of mouse longevity and body weight genes.