Longitudinal analysis of body weight reveals homeostatic and adaptive traits linked to lifespan in diversity outbred mice

TL;DR

Tracking body weight over time in mice shows that maintaining stable weight is linked to longer lifespan and reveals new genetic factors related to aging.

Contribution

The study introduces novel heritable body weight traits associated with lifespan and identifies new genetic loci linked to energy homeostasis.

Findings

Ten body weight-derived traits were both heritable and associated with lifespan.

Five new genomic loci were identified that are linked to body weight dynamics and energy homeostasis.

Stable body weight maintenance was positively associated with lifespan in an age-dependent manner.

Abstract

Dense temporal measurements of physiological health, using simple and consistent assays, are essential to characterize biological processes associated with aging and evaluate the effectiveness of interventions on these processes. We measured body weight in 960 genetically diverse female mice, every 7-10 days over the full course of their lifespan. We used a state space model to characterize the trajectories of body weight throughout life and derived novel traits capturing the dynamics of body weight, 10 of which were both heritable and associated with lifespan. Genetic mapping of these body weight-derived traits identified 5 genomic loci, none of which were previously mapped to body weight. We observed that the ability to maintain stable body weight, despite fluctuations in energy intake and expenditure, was positively associated with lifespan in an age-dependent manner and mapped to a genomic locus linked to energy homeostasis. Our results highlight how dense longitudinal measurements of physiological phenotypes offer new insights into the biology of aging.

This study reveals that the ability to maintain a stable body weight predicts longevity in mice. By tracking weight dynamics throughout life, the authors identify genetic loci linked to body weight, energy homeostasis and healthy aging.

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