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

Alan Kavšek, Jérôme Salignon, Lluís Millan-Ariño, Patryk Marcinkowski, Ilke Sen and Christian G. Riedel ()
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Alan Kavšek: Karolinska Institute
Jérôme Salignon: Karolinska Institute
Lluís Millan-Ariño: Karolinska Institute
Patryk Marcinkowski: Karolinska Institute
Ilke Sen: Karolinska Institute
Christian G. Riedel: Karolinska Institute

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-61786-y

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