Zampieri Michele, Ciccarone Fabio, Calabrese Roberta, Franceschi Claudio, Bürkle Alexander, Caiafa Paola
Department of Cellular Biotechnologies and Hematology, "Sapienza" University of Rome, Rome 00161, Italy; Pasteur Institute-Fondazione Cenci Bolognetti, Rome 00161, Italy.
Department of Experimental Pathology, Alma Mater Studiorum, University of Bologna, Bologna 40126, Italy.
Mech Ageing Dev. 2015 Nov;151:60-70. doi: 10.1016/j.mad.2015.02.002. Epub 2015 Feb 20.
A complex interplay between multiple biological effects shapes the aging process. The advent of genome-wide quantitative approaches in the epigenetic field has highlighted the effective impact of epigenetic deregulation, particularly of DNA methylation, on aging. Age-associated alterations in DNA methylation are commonly grouped in the phenomenon known as "epigenetic drift" which is characterized by gradual extensive demethylation of genome and hypermethylation of a number of promoter-associated CpG islands. Surprisingly, specific DNA regions show directional epigenetic changes in aged individuals suggesting the importance of these events for the aging process. However, the epigenetic information obtained until now in aging needs a re-consideration due to the recent discovery of 5-hydroxymethylcytosine, a new DNA epigenetic mark present on genome. A recapitulation of the factors involved in the regulation of DNA methylation and the changes occurring in aging will be described in this review also considering the data available on 5 hmC.
多种生物学效应之间的复杂相互作用塑造了衰老过程。表观遗传学领域全基因组定量方法的出现凸显了表观遗传失调,尤其是DNA甲基化对衰老的实际影响。与年龄相关的DNA甲基化改变通常被归类为“表观遗传漂变”现象,其特征是基因组逐渐广泛去甲基化以及一些启动子相关的CpG岛发生高甲基化。令人惊讶的是,特定的DNA区域在老年个体中表现出定向的表观遗传变化,这表明这些事件对衰老过程的重要性。然而,由于最近发现了5-羟甲基胞嘧啶(一种存在于基因组上的新的DNA表观遗传标记),目前在衰老研究中获得的表观遗传信息需要重新审视。本综述将描述参与DNA甲基化调控的因素以及衰老过程中发生的变化,同时也会考虑关于5-羟甲基胞嘧啶的现有数据。