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Free keywords:
Animals
Caenorhabditis elegans/*genetics
Caenorhabditis elegans Proteins/*genetics
Cholestenes/metabolism
Chromatin/genetics
Histone Demethylases/*genetics
Histones/genetics
Longevity/*genetics
Methylation
Mutation/*genetics
Signal Transduction/genetics
Abstract:
Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension.