학술논문

Gene-by-environment modulation of lifespan and weight gain in the murine BXD family
Document Type
Original Paper
Source
Nature Metabolism. 3(9):1217-1227
Subject
Language
English
ISSN
2522-5812
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.
Roy et al. quantify the impact of a high-fat diet across genetically diverse strains of mice, revealing a generally negative effect on lifespan but also a wide variability.