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

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.

Automated summary

Through experiments on female mice, this study found that a high-fat diet can significantly shorten lifespan. Initial body weight and weight gain are important factors affecting longevity, while the response to a high-fat diet is modulated by gene-environment interactions. Classic serum metabolites may not be strong predictors of longevity.