frpr-18, a neuropeptide receptor, regulates organismal lifespan and stress tolerance in C. elegans

The mechanisms underlying neuropeptide signaling regulation of lifespan in Caenorhabditis elegans ( C. elegans ) remain unclear. FRPR-18 is a mammalian orexin/hypocretin-like receptor and modulates C. elegans arousal behavior by acting as a receptor for FLP-2 neuropeptide signaling, which is also associated with the systemic activation of the mitochondrial unfolded protein response (mitoUPR). Here we report our preliminary findings on the role of the frpr-18 gene in regulating lifespan and healthspan parameters, including stress resistance. Our results showed that frpr-18(ok2698) null mutants had a shorter lifespan and reduced survivability against thermal stress and paraquat treatment. On the other hand, loss of flp-2 function did not affect lifespan or paraquat tolerance but was necessary for normal thermal stress tolerance. These findings suggest that frpr-18 could play a role in regulating lifespan and stress resistance, possibly through flp-2 independent or parallel neuropeptide signaling pathways.