sir-2.1;utx-1

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Genetic mutants with sir-2.1, utx-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)
23.87
Lifespan change (compared to wild type)
46.17%
Lifespan comparisons
Double mutant sir-2.1(ok434);utx-1(RNAi) has a lifespan of 23.87 days, while single mutant sir-2.1(ok434) has a lifespan of 21.33 days and wild type has a lifespan of 16.33 days.
Type of interaction
See methods
Almost additive (positive)
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)
24.72
Lifespan change (compared to wild type)
52.97%
Lifespan comparisons
Double mutant sir-2.1(ok434);utx-1(RNAi) has a lifespan of 24.72 days, while single mutant sir-2.1(ok434) has a lifespan of 20.39 days and wild type has a lifespan of 16.16 days.
Type of interaction
See methods
Synergistic (positive)
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: sir-2.1 utx-1

Entrez ID
Symbol
GenAge
Wormbase ID

177924
sir-2.1
View on GenAge (sir-2.1)
WBGene00004800

NAD-dependent protein deacetylase sir-2.1;yeast SIR related

Locus: CELE_R11A8.4

Wormbase description: sir-2.1 encodes an NAD-dependent protein deacetylase with similarity to Saccharomyces cerevisiae Sir2p and mammalian SIRT1.

Entrez ID
Symbol
GenAge
Wormbase ID

181110
utx-1
View on GenAge (utx-1)
WBGene00017046

human UTX (Ubiquitously transcribed TPR on X) homolog

Locus: CELE_D2021.1

Wormbase description: utx-1 encodes a putative histone H3 di/trimethyllysine-27 (H3K27me2/me3) demethylase, required for embryonic viability and vulval development, and for high brood sizes, locomotion, and growth sizes; UTX-1 contains a JmjC domain, is orthologous to human UTX and UTY, and is paralogous to human JMJD3; by orthology, UTX-1 is expected to antagonize transcriptional repression by polycomb repressor complexes, which mark stem cells (and presumably germline) by H3K27me3-mediated repression of somatic genes.

Orthologs of sir-2.1;utx-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of sir-2.1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Sirt1

Orthologs of utx-1 in SynergyAge

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Species	Gene