DNA methylation dynamics in aging: how far are we from understanding the mechanisms?
DNA methylation dynamics in aging: how far are we from understanding the mechanisms?
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DOI：
10.1016/j.mad.2017.12.002
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发表时间：
2018-09-01
影响因子：
5.3
通讯作者：
Zampieri, Michele
中科院分区：
文献类型：
--
作者：
Ciccarone, Fabio;Tagliatesta, Stefano;Zampieri, Michele
DNA甲基化是目前最有希望监测衰老和预测预期寿命的分子标记。然而，与年龄相关的DNA甲基化变化的机制仍未被发现。在此，我们讨论了哺乳动物DNA表观基因组景观动态性质的现有知识，并提出了与衰老相关的DNA表观遗传变化的假定分子机制。具体来说，我们描述了甲基胞嘧啶及其氧化衍生物与染色质结构动力学、组蛋白翻译后修饰及其调节剂的年龄相关变化。最后，我们提出了一个概念框架，可以解释年龄对DNA甲基化模式影响的复杂性。这结合了DNA甲基化噪音的积累，以及所有可预测的、特定位点的DNA甲基化变化。收集这方面的信息将为未来的研究铺平道路，旨在建立表观遗传机制在衰老中的可能致病作用。
DNA methylation is currently the most promising molecular marker for monitoring aging and predicting life expectancy. However, the mechanisms underlying age-related DNA methylation changes remain mostly undiscovered.Here we discuss the current knowledge of the dynamic nature of DNA epigenome landscape in mammals, and propose putative molecular mechanisms for aging-associated DNA epigenetic changes. Specifically, we describe age-related variations of methylcytosine and its oxidative derivatives in relation to the dynamics of chromatin structure, histone post-translational modifications and their modulators.Finally, we are proposing a conceptual framework that could explain the complex nature of the effects of age on DNA methylation patterns. This combines the accumulation of DNA methylation noise and also all of the predictable, site-specific DNA methylation changes.Gathering information in this area would pave the way for future investigation aimed at establishing a possible causative role of epigenetic mechanisms in aging.