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

Nat Aging. 2023 Aug;3(8):938-947. doi: 10.1038/s43587-023-00467-1. Epub 2023 Jul 27.


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 (UPRER) in peripheral tissues after xbp-1 splicing in neurons. This odorant-induced UPRER 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 UPRER activation upon 1-undecene exposure. Our data suggest that the cell non-autonomous UPRER 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins* / genetics
  • Longevity*
  • Transforming Growth Factor beta / metabolism
  • Unfolded Protein Response


  • Caenorhabditis elegans Proteins
  • Transforming Growth Factor beta