The G proteincoupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. We find that C. elegans longevity is regulated by a chemosensory GPCR STR2, expressed in AWC and ASI amphid sensory neurons. STR2 function is required at temperatures of 20°C and higher on standard Escherichia coli OP50 diet. Under these conditions, this neuronal receptor also controls health span parameters and lipid droplet (LD) homeostasis in the intestine. We show that STR2 regulates expression of delta9 desaturases,
fat5,
fat6 and
fat7, and of diacylglycerol acyltransferase dgat2. Rescue of the STR2 function in either AWC and ASI, or ASI sensory neurons alone, restores expression of
fat5, dgat2 and restores LD stores and longevity. Rescue of stored fat levels of GPCR mutant animals to wildtype levels, with low concentration of glucose, rescues its lifespan phenotype. In all, we show that neuronal STR2 GPCR facilitates control of neutral lipid levels and longevity in C. elegans.