Preservation of mitochondrial membrane potential is necessary for lifespan extension from dietary restriction.
Brandon J BerryEvan MjeldeFatima CarrenoKathryn GilhamEmily J HansonEmily NaMatt KaeberleinPublished in: GeroScience (2023)
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.