DNA methylation and cognitive aging.
DNA methylation and cognitive aging.
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DOI：
10.18632/oncotarget.4215
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发表时间：
2015-06-10
期刊：
影响因子：
--
通讯作者：
Xu X
中科院分区：
文献类型：
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作者：
Xu X
随着老年人口的不断增加，神经退行性疾病等与年龄相关的疾病的高发病率已成为公众关注的一个巨大问题。尤其是老年人及其家人患有严重的学习、行为和认知障碍。对于这种可怕的症状缺乏有效的治疗方法，这对认知衰老的生物学机制研究提出了很高的要求。表观遗传学是一个拓宽哺乳动物基因组蓝图维度的新兴领域。与遗传学不同，它不仅是可遗传的，而且是可逆的。最近的研究表明，DNA甲基化是主要的表观遗传机制之一，在年龄相关性神经退行性变和认知缺陷的发病机制中发挥着关键作用。在这篇综述中，我们讨论了与年龄相关的认知功能的进化知识和认知老化的潜在DNA甲基化机制。这表明DNA甲基化障碍可能是行为和认知相关神经退行性变的一个关键但可逆的机制。还简要讨论了在组织和单细胞水平以及在代表性尺度和全基因组单碱基分辨率上检测DNA甲基化模式的动态的方法。重要的是，提出了认知衰老研究中DNA甲基化机制的挑战，并提出了解决这些困难的可能方案。
With ever-increasing elder population, the high incidence of age-related diseases such as neurodegenerative disorders has turned out to be a huge public concern. Especially the elders and their families dreadfully suffer from the learning, behavioral and cognitive impairments. The lack of effective therapies for such a horrible symptom makes a great demanding for biological mechanism study for cognitive aging. Epigenetics is an emerging field that broadens the dimensions of mammalian genome blueprint. It is, unlike genetics, not only inheritable but also reversible. Recent studies suggest that DNA methylation, one of major epigenetic mechanisms, plays a pivotal role in the pathogenesis of age-related neurodegenerations and cognitive defects. In this review, the evolving knowledge of age-related cognitive functions and the potential DNA methylation mechanism of cognitive aging are discussed. That indicates the impairment of DNA methylation may be a crucial but reversible mechanism of behavioral and cognitive related neurodegeneration. The methods to examine the dynamics of DNA methylation patterns at tissue and single cell level and at the representative scale as well as the whole genome single base resolution are also briefly discussed. Importantly, the challenges of DNA methylation mechanism of cognitive aging research are brought up, and the possible solutions to tackle these difficulties are put forward.