worm lifespan assays were performed at 20c , without fudr , as described previously30 unless noted otherwise . for each lifespan assay , 90 worms per condition were used in three plates ( 30 worms per plate ) , except for the initial rnai screen , which was performed with 30 - 60 worms per condition . statistical analyses of lifespan were performed on kaplan - meier survival curves in statview 5.0.01 by logrank ( mantel - cox ) tests . for statistical comparison of independent replicates , fisher s combined probability tests were performed . to compare the interaction between genotype and rnai , two - way anova tests were performed . n2 ( wt ) and glp-1(e2141ts ) mutant worms were hatched at 16c and switched to bacteria with control empty vector ( e.v . ) or ash-2 rnai and moved to the restrictive temperature of 25.5c at the l1 stage . each condition was done in independent triplicate with ~1000 worms per triplicate for l3 worms , and ~200 worms picked every day after adulthood to fresh plates per triplicate for day 8 worms . microarray hybridization was performed at the stanford protein and nucleic acid facility with oligonucleotide arrays ( affymetrix , genechip c. elegans genome arrays ) . worm lifespan assays were performed at 20c , without fudr , as described previously30 unless noted otherwise . for each lifespan assay , 90 worms per condition were used in three plates ( 30 worms per plate ) , except for the initial rnai screen , which was performed with 30 - 60 worms per condition . statistical analyses of lifespan were performed on kaplan - meier survival curves in statview 5.0.01 by logrank ( mantel - cox ) tests . for statistical comparison of independent replicates , fisher s combined probability tests were performed . to compare the interaction between genotype and rnai , two - way anova tests were performed . n2 ( wt ) and glp-1(e2141ts ) mutant worms were hatched at 16c and switched to bacteria with control empty vector ( e.v . ) or ash-2 rnai and moved to the restrictive temperature of 25.5c at the l1 stage . each condition was done in independent triplicate with ~1000 worms per triplicate for l3 worms , and ~200 worms picked every day after adulthood to fresh plates per triplicate for day 8 worms . microarray hybridization was performed at the stanford protein and nucleic acid facility with oligonucleotide arrays ( affymetrix , genechip c. elegans genome arrays ) .
the plasticity of aging suggests that longevity may be controlled epigenetically by specific alterations in chromatin state . 
 the link between chromatin and aging has mostly focused on histone deacetylation by the sir2 family1,2 , but less is known about the role of other histone modifications in longevity . 
 histone methylation plays a crucial role during development and in maintaining stem cell pluripotency in mammals3 . 
 regulators of histone methylation have been associated with aging in worms4,5,6,7 and flies8 , but characterization of their role and mechanism of action has been limited . here 
 we identify the ash-2 trithorax complex9 , which trimethylates histone h3 at lysine 4 ( h3k4 ) , as a regulator of lifespan in c. elegans in a directed rnai screen in fertile worms . 
 deficiencies in members of the ash-2 complex 
 ash-2 itself , wdr-5 , and the h3k4 methyltransferase set-2 extend worm lifespan . 
 conversely , the h3k4 demethylase rbr-2 is required for normal lifespan , consistent with the idea that an excess of h3k4 trimethylation  a mark associated with active chromatin  is detrimental for longevity . 
 lifespan extension induced by ash-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs . 
 ash-2 and rbr-2 act in the germline , at least in part , to regulate lifespan and to control a set of genes involved in lifespan determination . 
 these results suggest that the longevity of the soma is regulated by an h3k4 methyltransferase / demethylase complex acting in the c. elegans germline .