Reverse electron transfer is activated during aging and contributes to aging and age-related disease.

ABSTRACT: Mechanisms underlying the depletion of NAD⁺ and accumulation of reactive oxygen species (ROS) in aging and age-related disorders remain poorly defined. We show that reverse electron transfer (RET) at mitochondrial complex I, which causes increased ROS production and NAD⁺ to NADH conversion and thus lowered NAD⁺ /NADH ratio, is active during aging. Genetic or pharmacological inhibition of RET decreases ROS production and increases NAD⁺ /NADH ratio, extending the lifespan of normal flies. The lifespan-extending effect of RET inhibition is dependent on NAD⁺ -dependent Sirtuin, highlighting the importance of NAD⁺ /NADH rebalance, and on longevity-associated Foxo and autophagy pathways. RET and RET-induced ROS and NAD⁺

SUBMITTER: Rimal S 

PROVIDER: S-EPMC10074108 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature