Neural G protein-coupled receptor OCTR-1 mediates temperature effects on longevity by regulating immune response genes in C. elegans

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{degrees}C, octr-1(ok371) mutant animals have similar lifespan to wild-type N2 animals. However, at higher temperature 25{degrees}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{degrees}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.