Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.
Bottom Line: Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation.The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants.Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression.
Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.Show MeSH
Mentions: We next asked if a transgenerational epigenetic heritability of lifespan was also observed with SET-2, the H3K4me3 methyltransferase enzyme that functions together with ASH-2 and WDR-5 to regulate H3K4me3 levels12,20–22 and longevity in C. elegans12 (Fig. 2). Similar to what we observed for wdr-5, genetically wildtype descendents from set-2(ok952) mutants still exhibited a ~30% extension of lifespan (p<0.0001) in the F3 and F4 generations (Fig. 2b, c), but not in the F5 generation (Fig. 2d). Genetically wildtype F3 descendents from the reverse cross – P0 set-2(ok952) males crossed with wildtype hermaphrodites – were also long-lived (Supplementary Table 1), indicating that transgenerational inheritance of longevity is not linked to a particular gender in the parental generation.
Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.