Sex- and age-dependent genetics of longevity in a heterogeneous mouse population-Reference-Cited by-同舟云学术

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

Published:2022-09-30 Issue:6614 Volume:377 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Bou Sleiman Maroun¹^ORCID,Roy Suheeta²^ORCID,Gao Arwen W.¹^ORCID,Sadler Marie C.³⁴⁵^ORCID,von Alvensleben Giacomo V. G.¹^ORCID,Li Hao¹^ORCID,Sen Saunak⁶^ORCID,Harrison David E.⁷,Nelson James F.⁸,Strong Randy⁸⁹^ORCID,Miller Richard A.¹⁰^ORCID,Kutalik Zoltán³⁴⁵^ORCID,Williams Robert W.²^ORCID,Auwerx Johan¹^ORCID

Affiliation:

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 38163, USA.

3. Institute of Primary Care and Public Health (Unisante), University of Lausanne, Lausanne 1011, Switzerland.

4. Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland.

5. Department of Computational Biology, University of Lausanne, Lausanne 1015, Switzerland.

6. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

7. The Jackson Laboratory, Bar Harbor, ME 04609, USA.

8. Barshop Center for Longevity Studies at the University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

9. South Texas Veterans Healthcare System, San Antonio, TX 78229, USA.

10. Department of Pathology, University of Michigan Geriatrics Center, Ann Arbor, MI 48109-2200, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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