ash-2;rrf-1

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Genetic mutants with ash-2, rrf-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Diet
HT115
Lifespan (days)
14.04
Lifespan change (compared to wild type)
28.22%
Lifespan comparisons
Double mutant ash-2(RNAi);rrf-1(ok589) has a lifespan of 14.04 days, while single mutant ash-2(RNAi) has a lifespan of 20.76 days, single mutant rrf-1(ok589) has a lifespan of 12.15 days and wild type has a lifespan of 10.95 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Jin C et al., 2011, Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab. 14(2):161-72 21803287 Click here to select all mutants from this PubMed ID in the graph
Abstract
Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

Temperature °C
20
Diet
HT115
Lifespan (days)
15.3
Lifespan change (compared to wild type)
39.73%
Lifespan comparisons
Double mutant ash-2(RNAi);rrf-1(ok589) has a lifespan of 15.3 days, while single mutant ash-2(RNAi) has a lifespan of 20.76 days, single mutant rrf-1(ok589) has a lifespan of 12.3 days and wild type has a lifespan of 10.95 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Jin C et al., 2011, Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab. 14(2):161-72 21803287 Click here to select all mutants from this PubMed ID in the graph
Abstract
Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

Temperature °C
20
Diet
HT115
Lifespan (days)
14.57
Lifespan change (compared to wild type)
33.06%
Lifespan comparisons
Double mutant ash-2(RNAi);rrf-1(ok589) has a lifespan of 14.57 days, while single mutant ash-2(RNAi) has a lifespan of 20.76 days, single mutant rrf-1(ok589) has a lifespan of 11.91 days and wild type has a lifespan of 10.95 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Jin C et al., 2011, Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab. 14(2):161-72 21803287 Click here to select all mutants from this PubMed ID in the graph
Abstract
Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

Search genes: ash-2 rrf-1

Entrez ID
Symbol
GenAge
Wormbase ID

174838
ash-2
View on GenAge (ash-2)
WBGene00012458

ASH histone methyltransferase complex subunit (Drosophila absent, small or homeotic discs);Set1/Ash2 histone methyltransferase complex subunit ash-2

Locus: CELE_Y17G7B.2

Wormbase description: ash-2 encodes the C. elegans ortholog of Drosophila Ash2, a trithorax group protein that is a member of the conserved H3K4 trimethylation (H3K4me3) complex; in C. elegans, loss of ash-2 via RNAi results in reduced levels of H3K4me3 at L3 larval stages indicating that ASH-2 functions in H3K4 trimethylation; ASH-2 also functions in the C. elegans germline to negatively regulate lifespan; in addition, loss of ash-2 activity via RNAi results in embryonic lethality characterized by defects in cortical activity and spindle rocking; loss of ash-2 activity in a lin-35 mutant background results in reduced brood size and lethality; two ash-2 deletion mutations, tm1903 and tm1905, also result in lethality and sterility; ASH-2 is highly expressed in the germ line and in early embryos; ASH-2 localizes to the nucleus.

Entrez ID
Symbol
GenAge
Wormbase ID

172523
rrf-1
View on GenAge (rrf-1)
WBGene00004508

RNA-dependent RNA polymerase Family

Locus: CELE_F26A3.8

Wormbase description: rrf-1 encodes an RNA-directed RNA polymerase (RdRP) homolog required for somatic (but not germline) RNAi; RRF-1 is also required for 'transitive interference'.

Orthologs of ash-2;rrf-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of ash-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ash2l

Orthologs of rrf-1 in SynergyAge

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Species	Gene