LIN-39 is a neuron-specific developmental determinant of longevity in Caenorhabditis elegans with reduced insulin...

The nuclear chromatin landscape changes with age. Here, we investigate whether chromatin alterations distinguish also animals with unusual aging rates, focusing on Caenorhabditis elegans with reduced insulin/IGF-like signaling (IIS), i.e., daf-2 mutants. In these animals, enhancer regions that close with age tend to open and become transcriptionally active. We identify LIN-39 as a transcription factor (TF) binding these regions and being required for the longevity of daf-2 mutants. LIN-39 acts during late development in hermaphrodite-specific VC motor neurons - at a time when these undergo maturation. LIN-39-mediated longevity requires DAF-16/FOXO, suggesting cooperation of both TFs in VC neurons to open enhancers. Our findings argue that longevity of daf-2 mutant hermaphrodites relies on a signal emitted by properly matured VC neurons, and due to its essential role in this maturation process LIN-39 becomes a rare example of a development-specific lifespan determinant.