Publication

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

Résumé

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.

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Concepts associés (32)
Genetic variation
Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources of genetic variation, but other mechanisms, such as genetic drift, contribute to it, as well. Genetic variation can be identified at many levels. Identifying genetic variation is possible from observations of phenotypic variation in either quantitative traits (traits that vary continuously and are coded for by many genes (e.
Human genetic variation
Human genetic variation is the genetic differences in and among populations. There may be multiple variants of any given gene in the human population (alleles), a situation called polymorphism. No two humans are genetically identical. Even monozygotic twins (who develop from one zygote) have infrequent genetic differences due to mutations occurring during development and gene copy-number variation. Differences between individuals, even closely related individuals, are the key to techniques such as genetic fingerprinting.
Amaigrissement
Un amaigrissement est une perte de poids. Il témoigne d'un déséquilibre entre les apports et les dépenses énergétiques. Il peut être volontaire, avec un régime amaigrissant dans un but esthétique ou thérapeutique, ou involontaire, pouvant alors révéler certaines maladies organiques évolutives, ou des troubles du comportement alimentaire. Un poids normal et stable est l'un des meilleurs marqueurs d'un état de santé normal chez l’adulte. Entre 20 et 50 ans, le poids augmente physiologiquement puis se stabilise pour diminuer spontanément après 75 ans.
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