RRC ID 45791
Author Lin YH, Chen YC, Kao TY, Lin YC, Hsu TE, Wu YC, Ja WW, Brummel TJ, Kapahi P, Yuh CH, Yu LK, Lin ZH, You RJ, Jhong YT, Wang HD.
Title Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans.
Journal Aging Cell
Abstract 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.
Volume 13(4)
Pages 755-64
Published 2014-8-1
DOI 10.1111/acel.12232
PMID 24889782
PMC PMC4116436
MeSH Adaptation, Physiological Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / physiology Drosophila melanogaster / enzymology* Drosophila melanogaster / physiology Epistasis, Genetic Gene Knockdown Techniques Lipoprotein Lipase / metabolism* Longevity* Mutation / genetics Oxidative Stress* Phosphorylation RNA Interference Ribosomal Protein S6 Kinases / metabolism Signal Transduction* TOR Serine-Threonine Kinases / metabolism*
IF 7.238
Times Cited 25
C.elegans tm2908 tm3026