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

Abstract

Animals rely on chemosensory cues to survive in pathogen-rich environments. InC. elegans, pathogenic bacteria are known to trigger aversive behaviors through neuronal perception, and to activate molecular defenses throughout the animal. This suggests that neurons may be able to coordinate the activation of organism-wide defensive responses upon pathogen perception. We find that exposure to volatile pathogen-associated compounds induces cell non-autonomous activation of the endoplasmic reticulum unfolded protein response (UPRER) in peripheral tissues followingxbp-1splicing in neurons. This odorant-induced UPRERactivation is dependent upon transforming growth factor beta (TGF-β) signaling and leads to extended lifespan and enhanced clearance of toxic proteins. Our data suggest that the cell non-autonomous UPRERrewires organismal proteostasis in response to pathogen detection, pre-empting the arrival of proteotoxic stress. Thus, chemosensation of particular odors may be a novel way to manipulate stress responses and longevity.

P. aeruginosacontrols bothC. elegansattraction and pathogenesis by regulating nitrogen assimilation

“…Some previous studies have examined molecules that are produced by P. aeruginosa and sensed by C. elegans. These studies identified several compounds that are repulsive to C. elegans and one molecule that is attractive, but without being able to eliminate production of these molecules from the bacteria, the actual activity of these molecules remained unclear 8,9,11,35 . Excitingly, we identified the nitrogen assimilation product, ammonia, as the major attractant that causes C. elegans to prefer P. aeruginosa over E. coli .…”

“…C. elegans respond and chemotax toward volatile compounds using olfactory neurons that control their locomotion 4 . A number of C. elegans attractants and repellents have been defined, and some of these attractants and repellants have been shown to be produced by bacteria [4][5][6][7][8][9] . But the physiological importance of the production of specific bacterially-produced molecules for the chemotaxis of C. elegans towards specific bacterial species has remained largely elusive.…”

“…One example of the complex responses of C. elegans to its environment is its multifaceted behaviors in the presence of the bacterium, Pseudomonas aeruginosa [8][9][10][11][12][13] .…”

A Year at the Forefront of Proteostasis and Aging

“…A new study has now observed that olfactory chemosensation of pathogen-derived molecules by chemosensory neurons cause cell non-autonomous activation of the UPR ER in C. elegans . This is accompanied by lifespan extension and reduced accumulation of toxic polyglutamine expansions ( De-Souza et al, 2022a preprint). In parallel, another group observed that exposure to a specific odour (urine) extends the lifespan of female mice ( Garratt et al, 2022 preprint).…”

“…However, this approach is difficult to tune and the blood–brain barrier is a major obstacle in efforts to manipulate neurons. Works showing that neuronal proteostasis can be modulated by sensory inputs ( De-Souza et al, 2022a preprint; Ozbey et al, 2020 ) suggest that, if validated in mammals, targeting chemosensory neurons could be a strategy to bypass the blood–brain barrier to modulate brain proteostasis.…”