The H3K27 demethylase UTX‐1 regulates C. elegans lifespan in a germline‐independent, insulin‐dependent manner
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Summary: Aging is accompanied by alterations in epigenetic marks that control chromatin states, including histone acetylation and methylation. Enzymes that reversibly affect histone marks associated with active chromatin have recently been found to regulate aging in Caenorhabditis elegans . However, relatively little is known about the importance for aging of histone marks associated with repressed chromatin. Here, we use a targeted RNAi screen in C. elegans to identify four histone demethylases that significantly regulate worm lifespan, UTX‐1, RBR‐2, LSD‐1, and T26A5.5. Interestingly, UTX‐1 belongs to a conserved family of histone demethylases specific for lysine 27 of histone H3 (H3K27me3), a mark associated with repressed chromatin. Both utx‐1 knockdown and heterozygous mutation of utx‐1 extend lifespan and increase the global levels of the H3K27me3 mark in worms. The H3K27me3 mark significantly drops in somatic cells during the normal aging process. UTX‐1 regulates lifespan independently of the presence of the germline, but in a manner that depends on the insulin‐FoxO signaling pathway. These findings identify the H3K27me3 histone demethylase UTX‐1 as a novel regulator of worm lifespan in somatic cells.
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Knockdown of H3K27me3 demethylase UTX-1 increases lifespan in C. elegans, suggesting H3K27me3 levels are beneficial for longevity.
“Knockdown of the H3K27me3 demethylase UTX-1 increases lifespan in C. elegans (Jin et al., 2011; Maures et al., 2011; Ni et al., 2012), suggesting that H3K27me3 levels are beneficial for longevity.”
From The Aging Epigenome (2016) · cites this paper as Maures et al., 2011
Age-associated changes in global H3K27me3 levels are context dependent.
“Interestingly, age-associated changes in global H3K27me3 levels are also context dependent.”
From The Aging Epigenome (2016) · cites this paper as Maures et al., 2011
Global H3K27me3 increases with age in killifish brain and mouse quiescent satellite cells but decreases during C. elegans aging and in human progeria models.
“Global H3K27me3 increases with age in the killifish brain and mouse quiescent satellite cells (Baumgart et al., 2014; Liu et al., 2013) but decreases with age during C. elegans aging and in human progeria models (Maures et al., 2011; Ni et al., 2012; Shumaker et al., 2006; Zhang et al., 2015b).”
From The Aging Epigenome (2016) · cites this paper as Maures et al., 2011
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- Authors
- Maures, T. J., Greer, E. L., Hauswirth, A. G., & Brunet, A.
- Affiliations
- Stanford University (US)
- Corresponding author
- Brunet, Anne
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2011-09-16
- Volume
- 10
- Issue
- 6
- Pages
- 980-990
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3215905
- OpenAlex
- W1508556872
- Cited by
- 256
- References
- 75
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 14 · 2023: 20 · 2022: 18 · 2021: 33 · 2020: 10 · 2019: 19 · 2018: 23 · 2017: 18 · 2016: 22 · 2015: 17 · 2014: 15 · 2013: 17 · 2012: 12
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R56AG031198, F32AG037254, AG31198, R01AG031198)
- National Human Genome Research Institute (T32HG000044)
- National Cancer Institute (T32CA009302)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- H3K27 demethylase, H3K27me3, histone demethylation, lifespan, aging, Caenorhabditis elegans, somatic cells, histone methylation
- MeSH terms
- Animals, Chromatin, Gene Expression Regulation, Germ Cells, Histones, Insulin, Longevity, Methylation, Transcription Factors, Blotting, Western, Signal Transduction, Biomarkers, Polymerase Chain Reaction, Caenorhabditis elegans, RNA Interference, Gene Knockdown Techniques, Histone Demethylases, High-Throughput Screening Assays
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