The cerebellum ages slowly according to the epigenetic clock.
The cerebellum ages slowly according to the epigenetic clock.
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DOI：
10.18632/aging.100742
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发表时间：
2015-05
期刊：
影响因子：
--
通讯作者：
Coles LS
中科院分区：
文献类型：
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作者：
Horvath S;Mah V;Lu AT;Woo JS;Choi OW;Jasinska AJ;Riancho JA;Tung S;Coles NS;Braun J;Vinters HV;Coles LS
阐明为什么某些人体组织比其他组织衰老得更快的研究可能会揭示我们是如何衰老的，并最终提出可能的干预措施。在这里，我们利用最近的衰老生物标志物（称为表观遗传时钟）来评估来自超级百岁老人（年龄达到110岁或以上的受试者）和年轻受试者的多达30个解剖部位的表观遗传年龄。使用三个新的和三个已发表的人类DNA甲基化数据集，我们证明小脑的年龄比人体的其他部位更慢。我们使用转录数据和遗传数据来阐明可能解释这一发现的分子机制。解旋酶的两个最大的超家族（SF1和SF2）在小脑中过表达的基因转录本中的比例明显高于（p=9.2×10−9）来自同一受试者的其他大脑区域。此外，与小脑表观遗传年龄加速相关的SNP往往位于解旋酶超家族SF1和SF2的基因附近（富集p=5.8×10−3）。我们对表观遗传年龄加速的遗传和转录研究支持了小脑缓慢衰老是由于RNA解旋酶参与的过程的假设。
Studies that elucidate why some human tissues age faster than others may shed light on how we age, and ultimately suggest what interventions may be possible. Here we utilize a recent biomarker of aging (referred to as epigenetic clock) to assess the epigenetic ages of up to 30 anatomic sites from supercentenarians (subjects who reached an age of 110 or older) and younger subjects. Using three novel and three published human DNA methylation data sets, we demonstrate that the cerebellum ages more slowly than other parts of the human body. We used both transcriptional data and genetic data to elucidate molecular mechanisms which may explain this finding. The two largest superfamilies of helicases (SF1 and SF2) are significantly over-represented (p=9.2×10−9) among gene transcripts that are over-expressed in the cerebellum compared to other brain regions from the same subject. Furthermore, SNPs that are associated with epigenetic age acceleration in the cerebellum tend to be located near genes from helicase superfamilies SF1 and SF2 (enrichment p=5.8×10−3). Our genetic and transcriptional studies of epigenetic age acceleration support the hypothesis that the slow aging rate of the cerebellum is due to processes that involve RNA helicases.