Metabotropic GABA signalling modulates longevity in C. elegans

Abstract The nervous system plays an important but poorly understood role in modulating longevity. GABA, a prominent inhibitory neurotransmitter, is best known to regulate nervous system function and behaviour in diverse organisms. Whether GABA signalling affects aging, however, has not been explored. Here we examined mutants lacking each of the major neurotransmitters in C. elegans , and find that deficiency in GABA signalling extends lifespan. This pro-longevity effect is mediated by the metabotropic GABA B receptor GBB-1, but not ionotropic GABA A receptors. GBB-1 regulates lifespan through G protein-PLCβ signalling, which transmits longevity signals to the transcription factor DAF-16/FOXO, a key regulator of lifespan. Mammalian GABA B receptors can functionally substitute for GBB-1 in lifespan control in C. elegans . Our results uncover a new role of GABA signalling in lifespan regulation in C. elegans , raising the possibility that a similar process may occur in other organisms.