It is shown here that the methylation of histone proteins regulates lifespan in Caenorhabditis elegans. Deficiencies in members of the ASH-2 complex, which trimethylates histone H3 at lysine 4 (H3K4), extend worm lifespan. Meanwhile, the H3K4 demethylase RBR-2 is required for normal lifespan. These findings are consistent with the idea that an excess of H3K4 trimethylation reduces longevity. The extension of lifespan caused by ASH-2 deficiency requires an intact adult germline and the continuous production of mature eggs.
- Eric L. Greer
- Travis J. Maures
- Anne Brunet