Temporally controlled nervous system-to-gut signaling bidirectionally regulates longevity in Caenorhabditis elegans

Xu, L.; Han, C.; Chun, L.; Xu, S.; Liu, J.

doi:10.1101/2024.04.12.589179

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bioRxiv · 10.1101/2024.04.12.589179

Temporally controlled nervous system-to-gut signaling bidirectionally regulates longevity in Caenorhabditis elegans

Xu, L.·Han, C.·Chun, L.·Xu, S.·Liu, J.

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Abstract

The nervous system modulates aging by secreting signaling molecules to cell-nonautonomously regulate the physiological state of distal tissues such as the gut. However, the underlying mechanisms are not well understood. Here, using C. elegans as a model, we identified two distinct neuroendocrine signaling circuits through which motor neurons signal the gut in early life to shorten lifespan but in mid-late life to extend lifespan. Both circuits employ the same neurotransmitter acetylcholine (ACh), while recruiting two different gut ACh receptors ACR-6 and GAR-3 to regulate the transcription factor DAF-16 and HSF-1 in early and mid-late life, respectively. Strikingly, the gut expression of ACR-6 is restricted to early life, whereas that of GAR-3 is confined to mid-late life, providing a potential mechanism for the temporal control of the two circuits. These results identify a novel mechanism that empowers the nervous system to bidirectionally regulate longevity by differentially signaling the gut at different life stages.

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Xu, L., Han, C., Chun, L., Xu, S., Liu, J.. 2024-04-15. Temporally controlled nervous system-to-gut signaling bidirectionally regulates longevity in Caenorhabditis elegans. https://doi.org/10.1101/2024.04.12.589179

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