Aging is associated with altered inflammatory, arachidonic acid cascade, and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex.
Aging is associated with altered inflammatory, arachidonic acid cascade, and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex.
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DOI：
10.1111/jnc.12153
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发表时间：
2013-04
影响因子：
4.7
通讯作者：
Rao JS
中科院分区：
文献类型：
--
作者：
Keleshian VL;Modi HR;Rapoport SI;Rao JS
衰老是阿尔茨海默病(AD)的危险因素，并与认知能力下降有关。然而，大脑老化的潜在分子机制尚不清楚。最近的研究表明，表观遗传学对阿尔茨海默病的基因表达有影响，因为DNA甲基化水平影响死后阿尔茨海默病脑内蛋白质和mRNA的表达。我们假设，其中一些变化发生在正常衰老的情况下。为了验证这一假设，我们测量了9名中年人(41±1岁)和10名老年人(70±3岁)死后额叶皮质花生四烯酸(AA)级联、神经炎症、促和抗凋亡因子以及基因特异性表观遗传修饰的标志物。老年组与中年组比较，神经炎性和AA级联标志物水平升高，促凋亡和抗凋亡因子改变，突触素丢失。其中一些变化与BDNF、CREB和突触素的启动子高甲基化和Bax的低甲基化有关。衰老过程中的这些分子变化不同于AD病理变化，或者比AD病理变化更微妙。它们在多大程度上与正常衰老过程中认知或行为的变化有关，仍有待评估。
Aging is a risk factor for Alzheimer’s disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, since DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged (41 ± 1 (SEM) years) and ten aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of BDNF, CREB, and synaptophysin and hypomethylation of BAX. These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated.
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影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0505394102
发表时间：
2005-08-30
影响因子：
11.1
作者：
Dong, E;Agis-Balboa, RC;Guidotti, A
通讯作者：
Guidotti, A
影响因子：
14.9
作者：
Dandekar, DH;Ganesh, KN;Mitra, D
通讯作者：
Mitra, D
影响因子：
15.1
作者：
Bollati, V.;Galimberti, D.;Pergoli, L.;Dalla Valle, E.;Barretta, F.;Cortini, F.;Scarpini, E.;Bertazzi, P. A.;Baccarelli, A.
通讯作者：
Baccarelli, A.
影响因子：
4.2
作者：
Bas, Orhan;Songur, Ahmet;Yagmurca, Murat
通讯作者：
Yagmurca, Murat