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Gap junctions in the C. elegans nervous system regulate ageing and lifespan

Vladis, N. A.; Fischer, K. E.; Digalaki, E.; Marcu, D.-C.; Nakos Bimpos, M.; Greer, P.; Ayres, A. I.; Li, Q.; Busch, K. E.

2019-06-02 physiology
10.1101/657817 bioRxiv
Show abstract

The nervous system is a central regulator of longevity, but how neuronal communication interfaces with ageing pathways is not well understood. Gap junctions are key conduits that allow voltage and metabolic signal transmission across cellular networks, yet it has remained unexplored whether they play a role in regulating ageing and longevity. We show that the innexin genes encoding gap junction subunits in Caenorhabditis elegans have extensive and diverse impacts on lifespan. Loss of the neural innexin unc-9 increases longevity by a third and also strongly benefits healthspan. Unc-9 acts specifically in a glutamatergic circuit linked to mechanosensation. Absence of unc-9 depends on a functional touch-sensing machinery to regulate lifespan and alters the age-dependent decline of mechanosensory neurons. The life extension produced by removal of unc-9 requires reactive oxygen species. Our work reveals for the first time that gap junctions are important regulators of ageing and lifespan.

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