Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction
Open accessAbstract
Aberrations in epigenetic marks have been associated with aging of the brain while caloric restriction (CR) and upregulation of endogenous antioxidants have been suggested as tools to attenuate the aging process. We have recently observed age-related increases in levels of 5-methylcytidine (5-mC) and DNA methyltransferase 3a (Dnmt3a) in the mouse hippocampus. Most of those age-related changes in these epigenetically relevant markers were prevented by CR but not by transgenic overexpression of the endogenous antioxidant superoxide dismutase 1 (SOD1). As recent work has suggested a distinct role for hydroxymethylation in epigenetic regulation of gene expression in the brain, the current study investigated age-related changes of 5-hydroxymethylcytosine (5-hmC) in the mouse hippocampus, and furthermore tested whether CR and transgenic upregulation of SOD1 affected any age-related changes in 5-hmC. Immunohistochemical analyses of 5-hmC in 12- and 24-month-old wild-type and transgenic mice overexpressing SOD1, which were kept under either a control or a calorie restricted diet, revealed an increase of 5-hmC immunoreactivity occurring with aging in the hippocampal dentate gyrus, CA3 and CA1-2 regions. Moreover, CR, but not overexpression of SOD1, prevented the age-related increase in the CA3 region. These findings indicate that the aging process in mice is connected with changes in epigenetic machinery in the hippocampus and suggest that CR acts by influencing epigenetic regulation.
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A calorie-restricted diet prevents age-related epigenetic and cellular changes.
“prevent age-related epigenetic 44–46 and cellular changes 47”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [45]
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- Authors
- Chouliaras, L., L.A. van den Hove, D., Kenis, G., Keitel, S., R. Hof, P., van Os, J., W.M. Steinbusch, H., Schmitz, C., & P.F. Rutten, B.
- Affiliations
- Maastricht University Medical Centre (NL)
- Anatomische Anstalt (DE)
- Corresponding author
- Chouliaras, Leonidas
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2012-05-02
- Volume
- 9
- Issue
- 5
- Pages
- 536-544
- ISSN
- 1567-2050 (ISSN-L)
- PMC
- PMC3561726
- OpenAlex
- W2017199534
- Cited by
- 91
- References
- 76
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 5 · 2019: 7 · 2018: 14 · 2017: 9 · 2016: 9 · 2015: 6 · 2014: 10 · 2013: 12 · 2012: 2
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (916.11.086)
- National Institute on Aging (P50 AG 05138, P50AG005138)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- 5-hydroxymethylcytosine, caloric restriction, hippocampus, brain aging, epigenetic regulation, superoxide dismutase 1, SOD1 overexpression, DNA hydroxymethylation, DNA methylation, DNMT3A, dentate gyrus, CA3 region, antioxidant defense
- MeSH terms
- Superoxide Dismutase-1, DNA Methyltransferase 3A, Age Factors, Animals, Cytosine, Gene Expression Regulation, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Superoxide Dismutase, Tissue Distribution, Caloric Restriction, 5-Methylcytosine, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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