Sex- and age-dependent genetics of longevity in a heterogeneous mouse population.

Document Type

Article

Publication Date

9-30-2022

Publication Title

Science

Keywords

JMG, Age Factors, Aging, Animals, Body Weight, Caenorhabditis elegans, Female, Humans, Longevity, Male, Mice, Quantitative Trait Loci, Sex Factors

JAX Source

Science. 2022;377(6614):eabo3191.

Volume

377

Issue

6614

First Page

3191

Last Page

3191

ISSN

1095-9203

PMID

36173858

DOI

https://doi.org/10.1126/science.abo3191

Grant

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.

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

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