Longevity is regulated by sensory experience, but the neural basis is incompletely understood. Previous studies have identified genes, neurons, and signals that maintain C. elegans lifespan at warmer temperature. Our previous work finds that the AFD thermosensory neuron secretes FLP-6, an FMRFamide neuropeptide essential for lifespan at warm temperature. Through screening C. elegans G-protein coupled receptors against a library of synthetic neuropeptides, we find that FRPR-8 is a likely candidate FLP-6 receptor. Lifespan reduction at warm temperature is observed in three
frpr-8 alleles, phenocopying the
flp-6 mutant. The
flp-6;
frpr-8 double mutant showed a life span similar to that of the
frpr-8 mutant, suggesting that
flp-6 and
frpr-8 function in the same genetic pathway. Furthermore,
frpr-8 mutations blocked the lifespan extension conferred by
flp-6 overexpression, suggesting that
frpr-8 acts downstream of
flp-6.
frpr-8 is expressed in the intestine as well as a few neurons, including the AWC and ASK chemosensory neurons, and the SIA and PVR interneurons. Although we failed to detect
frpr-8 expression in AIY interneuron, expression of
frpr-8 in the AIY interneuron, but not in the intestine or the ASK sensory neuron, fully rescued the short lifespan of the
frpr-8 mutant. Consistent with our previous finding that
flp-6 regulates longevity through
daf-16/FoxO, our double mutant analysis suggests that
frpr-8 and
daf-16 act in a common longevity pathway. Progress in this project will improve our understanding of the circuit basis for longevity response to warm temperature in C. elegans. (supported by National Health Research Institutes NHRI EX108-10830NI, the Ministry of Education MOE 107L9014, and the Ministry of Science and Technology, Taiwan MOST H77F/002, MOST 107-3017-F-002-002, MOST 107-2320-B-002-055-MY3).