TY - JOUR
T1 - Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction
AU - Chouliaras, Leonidas
AU - van den Hove, Daniel L. A.
AU - Kenis, Gunter
AU - Keitel, Stella
AU - Hof, Patrick R.
AU - van Os, Jim
AU - Steinbusch, Harry W. M.
AU - Schmitz, Christoph
AU - Rutten, Bart P. F.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Aging
KW - Epigenesis
KW - Epigenetics
KW - DNA methylation
KW - 5-methylcytidine (5-mC)
KW - Caloric restriction
KW - Antioxidants
KW - Superoxide dismutase (SOD)
KW - Hippocampus
U2 - 10.1016/j.neurobiolaging.2011.06.003
DO - 10.1016/j.neurobiolaging.2011.06.003
M3 - Article
C2 - 21764481
SN - 0197-4580
VL - 33
SP - 1672
EP - 1681
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 8
ER -