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.
Recommended Citation
Roy S,
Sleiman M,
Jha P,
Ingels J,
Chapman C,
McCarty M,
Ziebarth J,
Hook M,
Sun A,
Zhao W,
Huang J,
Neuner S,
Wilmott L,
Shapaker T,
Centeno A,
Ashbrook D,
Mulligan M,
Kaczorowski C,
Makowski L,
Cui Y,
Read R,
Miller R,
Mozhui K,
Williams E,
Sen S,
Lu L,
Auwerx J,
Williams R.
Gene-by-environment modulation of lifespan and weight gain in the murine BXD family. Nat Metab 2021 Sep; 3(9):1217-1227