Isocitrate Dehydrogenase Alpha-1 Modulates Lifespan and Oxidative Stress Tolerance in Caenorhabditis elegans

Altered metabolism is a hallmark of aging. The tricarboxylic acid cycle (TCA cycle) is an essential metabolic pathway and plays an important role in lifespan regulation. Supplementation of α-ketoglutarate, a metabolite converted by ( ) in the TCA cycle, increases lifespan in . However, whether can regulate lifespan in remains unknown. Here, we reported that the expression of modulates lifespan and oxidative stress tolerance in . Transgenic overexpression of extends lifespan, increases the levels of NADPH/NADP ratio, and elevates the tolerance to oxidative stress. Conversely, RNAi knockdown of exhibits the opposite effects. In addition, the longevity of mutant via dietary restriction (DR) was reduced by knockdown, indicating that may play a role in DR-mediated longevity. Furthermore, mediated lifespan may depend on the target of rapamycin (TOR) signaling. Moreover, the phosphorylation levels of S6 kinase (p-S6K) inversely correlate with expression, supporting that the -mediated lifespan regulation may involve the TOR signaling pathway. Together, our data provide new insights into the understanding of new function in lifespan regulation probably via DR and TOR signaling and in oxidative stress tolerance in .