Calorie Restriction Slows DNA Methylation in the Hippocampus

DNA methylation is proposed to be a good biomarker of aging, and here researchers show that calorie restriction slows the progression of DNA methylation in the hippocampus - continuing the expected trend of calorie restriction slowing near every identified biological change that occurs with aging: "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. ... These findings suggest a crucial role for DNA methylation in hippocampal aging and in the mediation of the beneficial effects of CR on aging."



I am curious to know whether epigenetic drift, which may be a significant cause of aging [see (*)], is accelerated by reduced activity of "maintenance" DNA-methyltransferases (Dnmt1) and increased activity of "de novo" DNA methyltransferases (Dnmt3a, Dnmt3b). After development is nearly complete, would such an imbalance would cause stem cells to lose their "stemness" and move tissue toward excessive differentiation and senescence?

(*)"Experimental Approaches to the Study of Epigenomic Dysregulation in Ageing"

Posted by: Lou Pagnucco at July 22nd, 2011 8:16 PM

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