CBP-1 acts in GABAergic neurons to double life span in axenically cultured Caenorhabditis elegans

When cultured in axenic medium, Caenorhabditis elegans shows the largest life-span extension compared with 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 life span 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 life span-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 life-span extension in axenic medium is under strict control of GABAergic neurons and may be linked to food sensing.