LAUSR

Dietary restriction (DR) increases lifespan in many organisms, but its underlying mechanisms are not fully understood. Mitochondria play a central role in metabolic regulation and are known to undergo changes in structure and function in response to DR. Mitochondrial membrane potential (Δψ_m) is the driving force for ATP production and mitochondrial outputs that integrate many cellular signals. One such signal regulated by Δψ_m is nutrient-status sensing. Here, we tested the hypothesis that DR promotes longevity through preserved Δψ_m during adulthood. Using the nematode Caenorhabditis elegans , we find that Δψ_m declines with age relatively early in the lifespan, and this decline is attenuated by DR. Pharmacologic depletion of Δψ_m blocked the longevity and health benefits of DR. Genetic perturbation of Δψ_m and mitochondrial ATP availability similarly prevented lifespan extension from DR. Taken together, this study provides further evidence that appropriate regulation of Δψ_m is a critical factor for health and longevity in response to DR.