Abstract
ABSTRACTDietary 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 (Δψm) is the driving force for ATP production and mitochondrial outputs that integrate many cellular signals. One such signal regulated by Δψmis nutrient-status sensing. Here, we tested the hypothesis that DR promotes longevity through preserved Δψmduring adulthood. Using the nematodeCaenorhabditis elegans, we find that Δψmdeclines with age relatively early in the lifespan, and this decline is attenuated by DR. Pharmacologic depletion of Δψmblocked the longevity and health benefits of DR. Genetic perturbation of Δψmand mitochondrial ATP availability similarly prevented lifespan extension from DR. Taken together, this study provides further evidence that appropriate regulation of Δψmis a critical factor for health and longevity in response to DR.
Publisher
Cold Spring Harbor Laboratory
Cited by
3 articles.
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