Abstract
Diacylglycerol (DAG) is a second messenger molecule which regulates several important cellular signaling pathways. Our previous study has isolated a long-lived mutant fly with up-regulation of diacylglycerol lipase (DAGL). In this thesis study, I followed up the C. elegans experiments by modulating DAGL expression and confirmed it affects lifespan and tolerance oxidative stress,and using this model I furtherstudy the underlying mechanisms. I investigated the two DAGL deleted mutants which show shorter lifespan, reduced tolerance to oxidative stress, and elevated level of lipid accumulation. Through genetic manipulation, I demonstrated that these phenotypes may result from the altered signaling of target of rapamycin (TOR) signaling pathways influenced by the levels of two DAG metabolites, 2-arachidonoyl glycerol (2-AG) and phosphatidic acid (PA). Furthermore, we found that intestine, the major tissue to store lipid in C. elegans, may be an important tissue for DAGL mediated lifespan and response to oxidative stress. These findings uncover new physiological roles of DAGL in modulating lifespan, oxidative stress resistance and lipid storage, and also indicate TOR signaling pathways as the possible molecular mechanisms of the DAGL-mediated physiological functions.