嗅覺透過神經胜肽調控線蟲壽命之神經迴路機轉

Abstract

我們發現失去FLP-6的線蟲在低溫環境中壽命變長，而且FLP-6作用在嗅覺神經AWC中限制壽命，FLP-6也對線蟲趨向由AWC神經元偵測的氣味的行為相當重要，而食物的味道則可以刺激FLP-6從AWC神經元釋放。在沒有食物的情況下，失去FLP-6的線蟲和wild type的線蟲壽命長度相同。利用mRNA 定序，我們發現FLP-6在不同培養溫度下調控兩群幾乎完全不同的基因群，再度驗證了FLP-6在不同神經元中有截然不同的功能。本篇研究描述了FLP-6在調控線蟲壽命中的角色。

Lifespan is 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, an FMRFamide-like neuropeptide, functions in the AFD thermosensory neurons to maintain lifespan at warmer temperature, and the flp-6 mutant is short-lived at 25°C. Here we find that the flp-6 mutant has extended lifespan at lower temperature, and that flp-6 acts in the AWC olfactory neurons to restrict lifespan, a conclusion further supported by requirement of flp-6 for chemotaxis towards AWC odorants. Exposure to bacterial food cues increases FLP-6 secretion from AWC, and the flp-6 mutation does not further extend lifespan of food-deprived animals. Gene expression profiling by mRNA-sequencing 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. These findings expand the known roles of FLP-6 in longevity control.