akt-2;utx-1

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Genetic mutants with akt-2, 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)
18.23
Lifespan change (compared to wild type)
11.64%
Phenotype
The life span extension by utx-1 RNAi was also abolished in three other mutants akt-1(ok525), akt-2(ok393), sgk-1(ok538), which are defective in the IIS pathway
Lifespan comparisons
Double mutant akt-2(ok393);utx-1(RNAi) has a lifespan of 18.23 days, while single mutant utx-1(RNAi) has a lifespan of 19.06 days, single mutant akt-2(ok393) has a lifespan of 18.0 days and wild type has a lifespan of 16.33 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)
21.77
Lifespan change (compared to wild type)
34.72%
Phenotype
The life span extension by utx-1 RNAi was also abolished in three other mutants akt-1(ok525), akt-2(ok393), sgk-1(ok538), which are defective in the IIS pathway
Lifespan comparisons
Double mutant akt-2(ok393);utx-1(RNAi) has a lifespan of 21.77 days, while single mutant utx-1(RNAi) has a lifespan of 19.18 days, single mutant akt-2(ok393) has a lifespan of 24.63 days and wild type has a lifespan of 16.16 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: akt-2 utx-1

Entrez ID
Symbol
GenAge
Wormbase ID

181524
akt-2
View on GenAge (akt-2)
WBGene00000103

Serine/threonine-protein kinase akt-2

Locus: CELE_F28H6.1

Wormbase description: akt-2 encodes a homolog of the serine/threonine kinase Akt/PKB, AKT-2, that is required for progression through the dauer stage of development and for the negative regulation of adult lifespan; inactivation of akt-2 causes animals to arrest constitutively at the dauer stage, while having an increased life span; widely expressed, AKT-2 is activated by the phospholipid products of phosphoinositide 3-kinase AGE-1/PI3K and by PDK-1, a homolog of vertebrate 3-phosphoinositide-dependent kinase-1 (PDK-1) Normal akt-2 (and akt-1) activity is required for excess pdk-1 activity to suppress the dauer-arrest phenotype of age-1, indicating that the 3-phosphoinositide-dependent kinase-1 homolog PDK-1 transduces signals from AGE-1 to AKT-2 (and AKT-1); conversely, the akt-2 loss-of-function phenotype is suppressed by daf-16 null mutations, indicating that the Fork head transcription factor DAF-16 is downstream of AKT-2 (and AKT-1), and that AKT-1 and AKT-2 act primarily to antagonize DAF-16.

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 akt-2;utx-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of akt-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1
Mus musculus	Akt1
Mus musculus	Akt2
Mus musculus	Akt3

Orthologs of utx-1 in SynergyAge

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Species	Gene