Limits...
Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A - Nature (2011)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.

Show MeSH
Genetically wildtype descendents from set-2 mutant parents have extended lifespan for several generationsa, Scheme for generating wildtype descendents from set-2(ok952) mutant worms. b–d, Lifespan of genetically wildtype F3 (b), F4 (c), and F5 (d) descendents from set-2(ok952) mutant worms (+/+ from P0 set-2 parents) compared to descendents of wildtype (N2) worms (+/+ from P0 N2 parents). Mean lifespan and statistics are presented in Supplementary Table 1.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368121&req=5

Figure 2: Genetically wildtype descendents from set-2 mutant parents have extended lifespan for several generationsa, Scheme for generating wildtype descendents from set-2(ok952) mutant worms. b–d, Lifespan of genetically wildtype F3 (b), F4 (c), and F5 (d) descendents from set-2(ok952) mutant worms (+/+ from P0 set-2 parents) compared to descendents of wildtype (N2) worms (+/+ from P0 N2 parents). Mean lifespan and statistics are presented in Supplementary Table 1.

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.


Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.

Greer EL, Maures TJ, Ucar D, Hauswirth AG, Mancini E, Lim JP, Benayoun BA, Shi Y, Brunet A - Nature (2011)

Genetically wildtype descendents from set-2 mutant parents have extended lifespan for several generationsa, Scheme for generating wildtype descendents from set-2(ok952) mutant worms. b–d, Lifespan of genetically wildtype F3 (b), F4 (c), and F5 (d) descendents from set-2(ok952) mutant worms (+/+ from P0 set-2 parents) compared to descendents of wildtype (N2) worms (+/+ from P0 N2 parents). Mean lifespan and statistics are presented in Supplementary Table 1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368121&req=5

Figure 2: Genetically wildtype descendents from set-2 mutant parents have extended lifespan for several generationsa, Scheme for generating wildtype descendents from set-2(ok952) mutant worms. b–d, Lifespan of genetically wildtype F3 (b), F4 (c), and F5 (d) descendents from set-2(ok952) mutant worms (+/+ from P0 set-2 parents) compared to descendents of wildtype (N2) worms (+/+ from P0 N2 parents). Mean lifespan and statistics are presented in Supplementary Table 1.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.

Show MeSH