The Caenorhabditis elegans neuronal GPCR OCTR-1 modulates longevity responses to both warm and cold temperatures

Many animal species live longer in cold climates than in warm climates, which was traditionally explained using the rate of living theory, i.e., higher temperatures increase chemical reaction rates, thus speeding up the aging process. However, recent studies have identified specific molecules and cells that are involved in longevity responses to temperature, indicating that such responses are not simply thermodynamic but are regulated processes. Here, we report that <i>Caenorhabditis elegans</i> lacking the neuronal G protein-coupled receptor OCTR-1 have extended lifespans at a warm temperature but shortened lifespans at a cold temperature, demonstrating that OCTR-1 modulates temperature-induced longevity responses. These responses are regulated by the OCTR-1-expressing, chemosensory ASH neurons. Furthermore, the OCTR-1 pathway controls such responses to warm and cold temperatures by regulating the expressions of immune response genes and the intestinal transcriptional factor ELT-2, respectively. Overall, our study provides cellular and molecular insights into the relationship between temperature and longevity.