Title

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family.

Document Type

Article

Publication Date

9-2021

Publication Title

Nat Metab

Keywords

JMG

JAX Source

Nat Metab 2021 Sep; 3(9):1217-1227

Volume

3

Issue

9

First Page

1217

Last Page

1227

ISSN

2522-5812

PMID

34552269

DOI

https://doi.org/10.1038/s42255-021-00449-w

Grant

AG054180

Abstract

How lifespan and body weight vary as a function of diet and genetic differences is not well understood. Here we quantify the impact of differences in diet on lifespan in a genetically diverse family of female mice, split into matched isogenic cohorts fed a low-fat chow diet (CD, n = 663) or a high-fat diet (HFD, n = 685). We further generate key metabolic data in a parallel cohort euthanized at four time points. HFD feeding shortens lifespan by 12%: equivalent to a decade in humans. Initial body weight and early weight gains account for longevity differences of roughly 4-6 days per gram. At 500 days, animals on a HFD typically gain four times as much weight as control, but variation in weight gain does not correlate with lifespan. Classic serum metabolites, often regarded as health biomarkers, are not necessarily strong predictors of longevity. Our data indicate that responses to a HFD are substantially modulated by gene-by-environment interactions, highlighting the importance of genetic variation in making accurate individualized dietary recommendations.

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