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

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 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 10 novel traits capturing the dynamics of body weight that are both associated with lifespan and heritable. Genetic mapping of these traits identified 12 genomic loci, none of which were previously mapped to body weight. We observed that the ability to stabilize body weight, despite fluctuations in energy intake and expenditure, is positively associated with lifespan and mapped to a genomic locus linked to energy homeostasis. Our results highlight the importance of dense longitudinal measurements of physiological traits for monitoring health and aging.