DNA methylation age of human tissues and cell types.
DNA methylation age of human tissues and cell types.
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DOI：
10.1186/gb-2013-14-10-r115
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Horvath S
中科院分区：
文献类型：
--
作者：
Horvath S
目前尚不清楚DNA甲基化水平是否可以用于准确预测广泛的人体组织和细胞类型的年龄，也不知道由此产生的年龄预测是否是一种具有生物学意义的测量方法。我开发了一种多组织年龄预测器，可以估计大多数组织和细胞类型的DNA甲基化年龄。该预测器可免费获得，使用来自82个Illumina DNA甲基化阵列数据集的8，000个样本开发，包括51种健康组织和细胞类型。我发现DNA甲基化年龄具有以下特性：首先，它对胚胎干细胞和诱导多能干细胞来说接近于零;其次，它与细胞传代次数相关;第三，它产生了一种高度可遗传的年龄加速措施;第四，它适用于黑猩猩组织。对来自32个数据集的6,000个癌症样本的分析表明，所有考虑的20种癌症类型都表现出明显的年龄加速，平均为36岁。癌症组织的低年龄加速与大量的体细胞突变和TP 53突变相关，而类固醇受体的突变大大加速了乳腺癌的DNA甲基化年龄。最后，我的353个CpG位点的特点，共同形成一个老化的时钟染色质状态和组织的变化。我建议DNA甲基化年龄测量表观遗传维持系统的累积效应。这种新的表观遗传时钟可用于解决发育生物学，癌症和衰老研究中的许多问题。
It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
4.5
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Grönniger E;Weber B;Heil O;Peters N;Stäb F;Wenck H;Korn B;Winnefeld M;Lyko F
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Lyko F
影响因子：
4.5
作者：
Christensen BC;Houseman EA;Marsit CJ;Zheng S;Wrensch MR;Wiemels JL;Nelson HH;Karagas MR;Padbury JF;Bueno R;Sugarbaker DJ;Yeh RF;Wiencke JK;Kelsey KT
通讯作者：
Kelsey KT
影响因子：
11.2
作者：
Fackler MJ;Umbricht CB;Williams D;Argani P;Cruz LA;Merino VF;Teo WW;Zhang Z;Huang P;Visvananthan K;Marks J;Ethier S;Gray JW;Wolff AC;Cope LM;Sukumar S
通讯作者：
Sukumar S
影响因子：
3.7
作者：
Bocklandt S;Lin W;Sehl ME;Sánchez FJ;Sinsheimer JS;Horvath S;Vilain E
通讯作者：
Vilain E