Open AccessDiacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in D rosophila and C . elegans
Author(s) -
Lin YenHung,
Chen YiChun,
Kao TzuYu,
Lin YiChun,
Hsu TzuEn,
Wu YiChun,
Ja William W.,
Brummel Theodore J.,
Kapahi Pankaj,
Yuh ChiouHwa,
Yu LinKwei,
Lin ZhiHan,
You RuJing,
Jhong YiTing,
Wang HorngDar
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12232
Subject(s) - diacylglycerol kinase , diacylglycerol lipase , biology , monoacylglycerol lipase , signal transduction , biochemistry , tor signaling , microbiology and biotechnology , oxidative stress , phosphatidic acid , protein kinase c , lipid metabolism , lipase , enzyme , endocannabinoid system , receptor , phospholipid , membrane
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 D rosophila and C aenorhabditis elegans, overexpression of diacylglycerol lipase ( DAGL / ina E / dagl‐1 ) or knockdown of diacylglycerol kinase ( DGK / rdgA / dgk‐5 ) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p‐ S 6 K ) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL / ina E / dagl‐1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p‐ S 6 K . Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S 6 K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging.