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


ABSTRACT: 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 isocitrate dehydrogenase alpha-1 (idha-1) in the TCA cycle, increases lifespan in C. elegans. However, whether idha-1 can regulate lifespan in C. elegans remains unknown. Here, we reported that the expression of idha-1 modulates lifespan and oxidative stress tolerance in C. elegans. Transgenic overexpression of idha-1 extends lifespan, increases the levels of NADPH/NADP+ ratio, and elevates the tolerance to oxidative stress. Conversely, RNAi knockdown of idha-1 exhibits the opposite effects. In addition, the longevity of eat-2 (ad1116) mutant via dietary restriction (DR) was reduced by idha-1 knockdown, indicating that idha-1 may play a role in DR-mediated longevity. Furthermore, idha-1 mediated lifespan may depend on the target of rapamycin (TOR) signaling. Moreover, the phosphorylation levels of S6 kinase (p-S6K) inversely correlate with idha-1 expression, supporting that the idha-1-mediated lifespan regulation may involve the TOR signaling pathway. Together, our data provide new insights into the understanding of idha-1 new function in lifespan regulation probably via DR and TOR signaling and in oxidative stress tolerance in C. elegans.

SUBMITTER: Lin ZH 

PROVIDER: S-EPMC9820670 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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<i>Isocitrate Dehydrogenase Alpha-1</i> Modulates Lifespan and Oxidative Stress Tolerance in <i>Caenorhabditis elegans</i>.

Lin Zhi-Han ZH   Chang Shun-Ya SY   Shen Wen-Chi WC   Lin Yen-Hung YH   Shen Chiu-Lun CL   Liao Sin-Bo SB   Liu Yu-Chun YC   Chen Chang-Shi CS   Ching Tsui-Ting TT   Wang Horng-Dar HD  

International journal of molecular sciences 20221229 1


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 <i>isocitrate dehydrogenase alpha-1</i> (<i>idha-1</i>) in the TCA cycle, increases lifespan in <i>C. elegans</i>. However, whether <i>idha-1</i> can regulate lifespan in <i>C. elegans</i> remains unknown. Here, we reported that the expression of <i>idha-1</i> modulat  ...[more]

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