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

Leonidas Chouliaras, Daniel L. A. van den Hove, Gunter Kenis, Stella Keitel, Patrick R. Hof, Jim van Os, Harry W. M. Steinbusch, Christoph Schmitz, Bart P. F. Rutten*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    59 Citations (Web of Science)

    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.
    Original languageEnglish
    Pages (from-to)536-544
    JournalCurrent Alzheimer Research
    Volume9
    Issue number5
    DOIs
    Publication statusPublished - Jun 2012

    Keywords

    • Aging
    • epigenesis
    • epigenetics
    • DNA hydroxymethylation
    • 5-hydroxymethylcytosine
    • caloric restriction
    • antioxidants
    • superoxide dismutase (SOD)
    • hippocampus

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