PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-2 (2)
 

Clipboard (0)
None

Select a Filter Below

Journals
Authors
Year of Publication
Document Types
1.  Age-related increase in levels of 5-hydroxymethylcytosine in mouse hippocampus is prevented by caloric restriction 
Current Alzheimer research  2012;9(5):536-544.
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 epigenetic 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 region-specific findings indicate that the aging process in mice is connected with epigenetic changes and suggest that the beneficial actions of CR may be mediated via epigenetic mechanisms such as methylation and hydroxymethylation of DNA.
PMCID: PMC3561726  PMID: 22272625
Aging; Epigenesis; Epigenetics; DNA hydroxymethylation; 5-hydroxymethylcytosine; Caloric restriction; Antioxidants; superoxide dismutase (SOD); Hippocampus
2.  Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction 
Neurobiology of Aging  2011;33(8):1672-1681.
Aberrant DNA methylation patterns have been linked to molecular and cellular alterations in the aging brain. Caloric restriction (CR) and upregulation of antioxidants have been proposed as interventions to prevent or delay age-related brain pathology. Previously, we have shown in large cohorts of aging mice, that age-related increases in DNA methyltransferase 3a (Dnmt3a) immunoreactivity in the mouse hippocampus were attenuated by CR, but not by overexpression of superoxide dismutase 1 (SOD1). Here, we investigated age-related alterations of 5-methylcytidine (5-mC), a marker of DNA methylation levels, in a hippocampal subregion-specific manner. Examination of 5-mC immunoreactivity in 12- and 24-month-old wild type (WT) mice on control diet, mice overexpressing SOD1 on control diet, wild type mice on CR, and SOD1 mice on CR, indicated an age-related increase in 5-mC immunoreactivity in the hippocampal dentate gyrus, CA3, and CA1–2 regions, which was prevented by CR but not by SOD1 overexpression. Moreover, positive correlations between 5-mC and Dnmt3a immunoreactivity were observed in the CA3 and CA1–2. These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging.
doi:10.1016/j.neurobiolaging.2011.06.003
PMCID: PMC3355211  PMID: 21764481
Aging; Epigenesis; Epigenetics; DNA methylation; 5-methylcytidine (5-mC); Caloric restriction; Antioxidants; Superoxide dismutase (SOD); Hippocampus

Results 1-2 (2)