Olfactory chemosensation extends lifespan through TGF-β signaling and UPR activation.

Animals rely on chemosensory cues to survive in pathogen-rich environments. In Caenorhabditis elegans, pathogenic bacteria trigger aversive behaviors through neuronal perception and activate molecular defenses throughout the animal. This suggests that neurons can coordinate the activation of organism-wide defensive responses upon pathogen perception. In this study, we found that exposure to volatile pathogen-associated compounds induces activation of the endoplasmic reticulum unfolded protein response (UPR ER ) in peripheral tissues after xbp-1 splicing in neurons. This odorant-induced UPR ER activation is dependent upon DAF-7/transforming growth factor beta (TGF-β) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Notably, rescue of the DAF-1 TGF-β receptor in RIM/RIC interneurons is sufficient to significantly recover UPR ER activation upon 1-undecene exposure. Our data suggest that the cell non-autonomous UPR ER rewires organismal proteostasis in response to pathogen detection, pre-empting proteotoxic stress. Thus, chemosensation of particular odors may be a route to manipulation of stress responses and longevity.