Sex- and age-dependent genetics of longevity in a heterogeneous mouse population
Abstract
DNA variants that modulate life span provide insight into determinants of health, disease, and aging. Through analyses in the UM-HET3 mice of the Interventions Testing Program (ITP), we detected a sex-independent quantitative trait locus (QTL) on chromosome 12 and identified sex-specific QTLs, some of which we detected only in older mice. Similar relations between life history and longevity were uncovered in mice and humans, underscoring the importance of early access to nutrients and early growth. We identified common age- and sex-specific genetic effects on gene expression that we integrated with model organism and human data to create a hypothesis-building interactive resource of prioritized longevity and body weight genes. Finally, we validated Hipk1, Ddost, Hspg2, Fgd6, and Pdk1 as conserved longevity genes using Caenorhabditis elegans life-span experiments.
From the paper
- Animals
This analysis was performed for a total of 1122 control mice of both sexes, which resulted in similar linkages to the analysis excluding litter size as a covariate, albeit with reduced significance (highest peak in females is at chromosome 3 with empirical p value = 0.399).
Results, Interplay between early growth, size, and longevity in mice and humans
- Result
… females have a higher median life span than males (female median = 886 days, 95% confidence interval (CI) [871–897], male median = 836 days, 95% CI [816–851]) …
Results, Multicenter and multiyear analysis identifies sex- and age-specific longevity loci
Quoted word for word from the full text on PubMed Central.
The paper
École Polytechnique Fédérale de Lausanne
Science, 30 Sep 2022, Open access