Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan.

Increased production of reactive oxygen species has long been considered a cause of aging. However, recent studies have implicated as essential secondary messengers. Here we show that the site of duanyu1670 production significantly contributes to their apparent dual nature. We report that duanyu1670 increase with age as mitochondrial function deteriorates. However, we also demonstrate that increasing duanyu1670 production specifically through respiratory complex I reverse electron transport extends Drosophila lifespan. Reverse electron transport rescued pathogenesis induced by severe oxidative stress, highlighting the importance of the site of duanyu1670 production in signaling. Furthermore, preventing ubiquinone reduction, through knockdown of PINK1, shortens lifespan and accelerates aging; phenotypes that are rescued by increasing reverse electron transport. These results illustrate that the source of a duanyu1670 signal is vital in determining its effects on cellular physiology and establish that manipulation of ubiquinone redox state is a valid strategy to delay aging.

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