Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction.
Prevention of age-related changes in hippocampal levels of 5-methylcytidine by caloric restriction.
复制标题
DOI：
10.1016/j.neurobiolaging.2011.06.003
复制
发表时间：
2012-08
影响因子：
4.2
通讯作者：
Rutten BP
中科院分区：
文献类型：
--
作者：
Chouliaras L;van den Hove DL;Kenis G;Keitel S;Hof PR;van Os J;Steinbusch HW;Schmitz C;Rutten BP
异常的DNA甲基化模式与衰老大脑中的分子和细胞变化有关。热量限制（CR）和抗氧化剂的上调已被提出作为干预措施，以预防或延缓与年龄相关的脑病理。之前，我们在衰老小鼠的大队列中发现，小鼠海马中DNA甲基转移酶3a （Dnmt3a）免疫反应性的年龄相关增加被CR减弱，但不被超氧化物歧化酶1 （SOD1）的过度表达减弱。在这里，我们以海马亚区特异性的方式研究了5-甲基胞苷（5-mC）的年龄相关变化，5-甲基胞苷是DNA甲基化水平的标志物。对12月龄和24月龄野生型（WT）小鼠、对照组过表达SOD1的小鼠、CR野生型小鼠和CR SOD1小鼠的5-mC免疫反应性检测表明，海马齿状回、CA3和CA1-2区域的5-mC免疫反应性随年龄的增加而增加，CR可以阻止这种增加，而SOD1过表达则不能。此外，在CA3和CA1-2中观察到5-mC与Dnmt3a免疫反应性呈正相关。这些发现表明DNA甲基化在海马衰老和CR对衰老的有益作用的中介中起着至关重要的作用。
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.
登录
查看更多内容
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
5.3
作者：
Adams, Michelle M.;Shi, Lei;Brunso-Bechtold, Judy K.
通讯作者：
Brunso-Bechtold, Judy K.
DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
影响因子：
3.7
作者：
Cao, Kajia;Chen-Plotkin, Alice S.;Wang, Li-San
通讯作者：
Wang, Li-San
影响因子：
--
作者：
Dickstein, Dara L.;Walsh, Jessica;Brautigam, Hannah;Stockton, Steven D., Jr.;Gandy, Samuel;Hof, Patrick R.
通讯作者：
Hof, Patrick R.