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Isocitrate Dehydrogenase Alpha-1 Modulates Lifespan and Oxidative Stress Tolerance in Caenorhabditis elegans.
Lin, Zhi-Han; Chang, Shun-Ya; Shen, Wen-Chi; Lin, Yen-Hung; Shen, Chiu-Lun; Liao, Sin-Bo; Liu, Yu-Chun; Chen, Chang-Shi; Ching, Tsui-Ting; Wang, Horng-Dar.
Afiliação
  • Lin ZH; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Chang SY; Institute of Chemistry, Academia Sinica, Taipei 115201, Taiwan.
  • Shen WC; Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, Academia Sinica, Taipei 115201, Taiwan.
  • Lin YH; Institute of Biochemical Sciences, National Taiwan University, Taipei 106319, Taiwan.
  • Shen CL; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Liao SB; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Liu YC; Institute of Biotechnology, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Chen CS; Department of Life Science, National Tsing Hua University, Hsinchu 300044, Taiwan.
  • Ching TT; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Wang HD; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
Int J Mol Sci ; 24(1)2022 Dec 29.
Article em En | MEDLINE | ID: mdl-36614054
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / Estresse Oxidativo / Proteínas de Caenorhabditis elegans / Isocitrato Desidrogenase / Longevidade Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caenorhabditis elegans / Estresse Oxidativo / Proteínas de Caenorhabditis elegans / Isocitrato Desidrogenase / Longevidade Limite: Animals Idioma: En Ano de publicação: 2022 Tipo de documento: Article