CBP-1 acts in GABAergic neurons to double lifespan in axenically cultured C. elegans.

When cultured in axenic medium, C. elegans shows the largest lifespan extension compared to other dietary restriction regimens. However, the underlying molecular mechanism still remains elusive. The gene cbp-1, encoding the worm ortholog of p300/CBP (CREB-binding protein), is one of the very few key genes known to be essential for lifespan doubling under axenic dietary restriction (ADR). By using tissue-specific RNAi, we found that cbp-1 expression in the germline is essential for fertility whereas this gene functions specifically in the GABAergic neurons to support the full lifespan-doubling effect of ADR. Surprisingly, GABA itself is not required for ADR-induced longevity, suggesting a role of neuropeptide signaling. In addition, chemotaxis assays illustrate that neuronal inactivation of CBP-1 affects the animals' food sensing behavior. Together, our results show that the strong lifespan extension in axenic medium is under strict control of GABAergic neurons and may be linked to food sensing.