Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans

Aging Cell

Yen-Hung Lin¹  Yi-Chun Chen¹  Tzu-Yu Kao¹  Yi-Chun Lin¹  Tzu-En Hsu¹  Yi-Chun Wu²  William W. Ja⁴  Theodore J. Brummel³  Pankaj Kapahi⁵  Chiou-Hwa Yuh⁶  Lin-Kwei Yu¹  Zhi-Han Lin¹  Ru-Jing You¹  Yi-Ting Jhong¹ 

[1] Institute of Biotechnology, National Tsing Hua University, HsinChu, Taiwan;Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan;Department of Biology, Long Island University, Brookville, NY, USA;Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL, USA;Buck Institute for Research on Aging, Novato, CA, USA;Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan

关键词: aging;    diacylglycerol;    diacylglycerol kinase;    metabolism;    phosphatidic acid;    S6 kinase;   

DOI  :  10.1111/acel.12232

来源: Wiley

【 摘 要 】

Summary

Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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