In Caenorhabditis elegans, functional ttx-3, sra-11, ceh-10, and ceh-23 genes are required for the functions of AIY interneuron. Compared to wild-type N2, mutations in ttx-3 and ceh-10 significantly decreased lifespan, whereas mutations in sra-11 and ceh-23 did not obviously influence nematode lifespan. Mutations in ttx-3 and ceh-10 were associated closely with lower pumping rates at adult day 8 and caused a more rapid accumulated intestinal autofluorescence than wild-type N2. Mutations in ceh-10 remarkably affected fertility and egg number in the uterus. The regulation of ttx-3 and ceh-10 on longevity was not temperature-dependent, and ttx-3, and ceh-10 mutants all formed very few dauers at 27°C. The shortened lifespan of the ttx-3 or ceh-10 mutants was completely or largely rescued by expression of TTX-3 or CEH-10 in AIY interneurons. Moreover, the long-lived phenotype of the daf-2 mutant could be suppressed by both the ttx-3 and the ceh-10 mutations. Furthermore, ablation of AIY interneurons shortened the longevity of wild-type and the daf-2 mutant. Therefore, ttx-3 and ceh-10 regulate the longevity through influencing the insulin/IGF signaling pathway in C. elegans.
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