Methylation of the ribosomal RNA gene promoter is associated with aging and age-related decline.
Methylation of the ribosomal RNA gene promoter is associated with aging and age-related decline.
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DOI：
10.1111/acel.12603
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发表时间：
2017-10
期刊：
影响因子：
7.8
通讯作者：
Passarino G
中科院分区：
文献类型：
--
作者：
D'Aquila P;Montesanto A;Mandalà M;Garasto S;Mari V;Corsonello A;Bellizzi D;Passarino G
核糖体RNA基因（rDNA）的转录受表观遗传调控，因为它被其启动子区域内CpG二核苷酸的甲基化所废除。在这里，我们通过Sequenom平台研究了472份20 - 105岁人类血液样本和15只3-96周龄大鼠不同组织（血液，心脏，肝脏，肾脏和睾丸）中落入rDNA启动子的CpG岛的年龄相关甲基化状态。在人类中，我们没有发现CpG位点甲基化与实际年龄之间存在一致的显著相关性。此外，在一项为期9年的随访研究中，其中一个分析的CpG位点的甲基化水平与认知能力和生存机会呈负相关。我们在重复样本中一致证实了这一结果。在大鼠中，对组织中同源区域的分析揭示了老年大鼠中甲基化增加的存在。在人类和大鼠中的rRNA表达数据与观察到的甲基化模式一致，在高度甲基化的样品中rRNA表达较低。由于特定品系大鼠的实足年龄和生物学年龄可能比人类更接近，这些结果似乎提供了第一个证据，即rDNA的表观遗传修饰随着时间的推移而变化。因此，rDNA的甲基化谱可能代表衰老的潜在生物标志物。
The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age‐related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20‐ to 105‐year‐old humans and in different tissues (blood, heart, liver, kidney, and testis) of 15 rats 3–96 weeks old. In humans, we did not find a consistently significant correlation between CpG site methylation and chronological age. Furthermore, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9‐year follow‐up study. We consistently confirmed such result in a replication sample. In rats, the analysis of the homologous region in the tissues revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with observed methylation patterns, with a lower expression of rRNA in highly methylated samples. As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNA may represent a potential biomarker of aging.
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