@article {Wibisono2021.05.07.443056, author = {Shawndra Wibisono and Phillip Wibisono and Jingru Sun}, title = {Neural G protein-coupled receptor OCTR-1 mediates temperature effects on longevity by regulating immune response genes in C. elegans}, elocation-id = {2021.05.07.443056}, year = {2021}, doi = {10.1101/2021.05.07.443056}, publisher = {Cold Spring Harbor Laboratory}, abstract = {We have previously demonstrated that OCTR-1, an octopamine G protein-couple receptor, functions in the sensory neurons ASH to suppress the innate immune response in Caenorhabditis elegans by inhibiting the expression of immune genes (Sun et al. 2011 Science 332:729-732). Here we discover that OCTR-1 also regulates temperature effects on lifespan in C. elegans. At the normal growth temperature 20{\textdegree}C, octr-1(ok371) mutant animals have similar lifespan to wild-type N2 animals. However, at higher temperature 25{\textdegree}C, octr-1(ok371) mutants live significant longer than wild-type N2 animals. These results suggest that OCTR-1 may mediate temperature effects on lifespan. Furthermore, we found the OCTR-1-expressing ASH chemosensory neurons are involved in the OCTR-1-mediated regulation on longevity. However, interestingly, the thermosensory AFD neurons do not play a role in this regulation at 25{\textdegree}C. RNA-seq data analysis showed that 63 immune response genes were significantly down-regulated in octr-1(ok371) mutants relative to wild-type animals at 25 C. We further demonstrated that inactivation of several most-downregulated genes by RNA interference in wild-type N2 animals significantly extended their lifespan, similar to the phenotype of octr-1(ok371) animals. These observations suggest a new molecular regulation mechanism that downregulation of immune genes extends the lifespan of C. elegans, which is opposite to the general belief that an increase in defense immunity extends lifespan.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2021/05/08/2021.05.07.443056}, eprint = {https://www.biorxiv.org/content/early/2021/05/08/2021.05.07.443056.full.pdf}, journal = {bioRxiv} }