Aging and lifespan are regulated by environmental factors, including temperature and food cues. The nervous system senses these environmental stimuli and releases signaling molecules, such as neuropeptides, to modulate longevity. We previously showed that FLP-6, a FMRFamide-like neuropeptide, functions in the AFD thermosensory neuron to maintain lifespan at warm temperature (25°C), and the
flp-6 mutant is short-lived at 25°C. Intriguingly, the
flp-6 mutant has extended lifespan at lower temperature (15°C), raising the possibility that FLP-6 also acts outside the thermosensory circuit. In addition to ASE gustatory neuron and AFD, we find that
flp-6 is also expressed in AWB and AWC olfactory neurons. The
flp-6 mutant has chemotaxis defects to odorants sensed by AWC. Furthermore, exposure to bacterial cues or butanone increases FLP-6 secretion from AWC. On the basis of these findings, we hypothesize that FLP-6 acts as a food-related signal secreted by the olfactory neurons to restrict lifespan. Deletion of
flp-6 in AWC by somatic CRISPR results in chemotaxis defects to butanone, suggesting that
flp-6 acts in AWC for chemotaxis to attractive odors. Gene expression profiling by mRNA-seq from animals cultivated at 15°C reveals sets of
flp-6-regulated genes that are distinct from those identified in animals cultivated at 25°C, confirming that
flp-6 has non-overlapping functions in different physiological contexts. We are currently defining the neuronal circuits in which
flp-6 may act to restrict lifespan in response to food stimuli and chemosensation. (This work is 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).