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

Maroun Bou Sleiman; Suheeta Roy; Arwen W. Gao; Marie C. Sadler; Giacomo V.G. von Alvensleben; Hao Li; Saunak Sen; David E. Harrison; James F. Nelson; Randy Strong; Richard A. Miller; Zoltán Kutalik; Robert W. Williams; Johan Auwerx

doi:10.1126/science.abo3191

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

Maroun Bou Sleiman, Suheeta Roy, Arwen W. Gao, Marie C. Sadler, Giacomo V.G. von Alvensleben, Hao Li, Saunak Sen, David E. Harrison, James F. Nelson, Randy Strong, Richard A. Miller, Zoltán Kutalik, Robert W. Williams, Johan Auwerx

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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.

Original language	English (US)
Article number	eabo3191
Journal	Science
Volume	377
Issue number	6614
DOIs	https://doi.org/10.1126/science.abo3191
State	Published - Sep 30 2022

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title = "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.",

author = "Sleiman, {Maroun Bou} and Suheeta Roy and Gao, {Arwen W.} and Sadler, {Marie C.} and {von Alvensleben}, {Giacomo V.G.} and Hao Li and Saunak Sen and Harrison, {David E.} and Nelson, {James F.} and Randy Strong and Miller, {Richard A.} and Zolt{\'a}n Kutalik and Williams, {Robert W.} and Johan Auwerx",

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doi = "10.1126/science.abo3191",

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AU - Sleiman, Maroun Bou

AU - Roy, Suheeta

AU - Gao, Arwen W.

AU - Sadler, Marie C.

AU - von Alvensleben, Giacomo V.G.

AU - Li, Hao

AU - Sen, Saunak

AU - Harrison, David E.

AU - Nelson, James F.

AU - Strong, Randy

AU - Miller, Richard A.

AU - Kutalik, Zoltán

AU - Williams, Robert W.

AU - Auwerx, Johan

PY - 2022/9/30

Y1 - 2022/9/30

N2 - 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.

AB - 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.

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

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