Cited by 91Epigenetics and DNA MethylationGenetics, Aging, and Longevity in Model OrganismsAntioxidants, Aging, Portulaca oleracea

Age-Related Increase in Levels of 5-Hydroxymethylcytosine in Mouse Hippocampus is Prevented by Caloric Restriction

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Chouliaras, Leonidas, L.A. van den Hove, Daniel, Kenis, Gunter, Keitel, Stella, R. Hof, Patrick, van Os, Jim, W.M. Steinbusch, Harry, Schmitz, Christoph +1 more·2012·Current Alzheimer Research

Abstract

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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  1. [41]Franklin KB Paxinos G The Mouse Brain in Stereotaxic Coordinates 1997 San Diego Academic Press

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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
Published
2012-05-02
Volume
9
Issue
5
Pages
536-544
ISSN
1567-2050 (ISSN-L)
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
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

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