Sex- and age-dependent genetics of longevity in a heterogeneous mouse population.
JMG, Age Factors, Aging, Animals, Body Weight, Caenorhabditis elegans, Female, Humans, Longevity, Male, Mice, Quantitative Trait Loci, Sex Factors
Ecole Polytechnique Fédérale de Lausanne (J.A.); European Research Council grant ERC-AdG-787702 (J.A.); Swiss National Science Foundation grant 31003A-179435 (J.A.); Swiss National Science Foundation grant 310030-189147 (Z.K.); National Institutes of Health grant AG043930 (R.W., J.A.); National Institutes of Health grant AG022303 (R.M.); National Institutes of Health grant AG022308 (D.H.); National Institutes of Health grant AG022307 (R.S.); Glenn Foundation for Medical Research (R.M.); R.S. is supported by a Senior Research Career Scientist Award from the Department of Veterans Affairs Office of Research and Development.
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
Bou Sleiman M,
von Alvensleben G,
Sex- and age-dependent genetics of longevity in a heterogeneous mouse population. Science. 2022;377(6614):eabo3191.