Cell and tissue type independent age-associated DNA methylation changes are not rare but common.
Cell and tissue type independent age-associated DNA methylation changes are not rare but common.
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与细胞和组织类型无关的、与年龄相关的 DNA 甲基化变化并不罕见，而是很常见。
DOI：
10.18632/aging.101666
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发表时间：
2018-11-27
期刊：
影响因子：
--
通讯作者：
Teschendorff AE
中科院分区：
文献类型：
--
作者：
Zhu T;Zheng SC;Paul DS;Horvath S;Teschendorff AE
在许多不同的组织和细胞类型中，年龄相关的DNA甲基化变化已被广泛报道。表观遗传“时钟”能够以惊人的高准确度预测实际年龄，似乎与组织和细胞类型无关，这表明表观遗传漂变的一个组成部分与细胞类型无关。然而，与年龄相关的dna变化的相对数量是特定于细胞或组织类型的，还是独立于细胞或组织类型的，目前尚不清楚，并且存在争议，最近的一项研究得出结论，大多数表观遗传漂变是组织特异性的。在这里，我们进行了一项新的综合统计分析，包括来自同一个体的匹配的多细胞型和多组织DNA甲基化谱，并调整了细胞型异质性，表明大量的表观遗传漂变（可能超过70%）在大量不同的组织/细胞类型之间共享。我们进一步表明，ELOVL2并不是唯一的，许多其他CpG位点，其中一些定位于Wnt和谷氨酸受体信号通路中的基因，在至少10种不同的细胞/组织类型中随着年龄的变化而改变。我们提出，虽然大多数与年龄相关的dna变化在细胞类型之间是共享的，但假定的功能影响可能是组织特异性的。
Age-associated DNA methylation changes have been widely reported across many different tissue and cell types. Epigenetic ‘clocks’ that can predict chronological age with a surprisingly high degree of accuracy appear to do so independently of tissue and cell-type, suggesting that a component of epigenetic drift is cell-type independent. However, the relative amount of age-associated DNAm changes that are specific to a cell or tissue type versus the amount that occurs independently of cell or tissue type is unclear and a matter of debate, with a recent study concluding that most epigenetic drift is tissue-specific. Here, we perform a novel comprehensive statistical analysis, including matched multi cell-type and multi-tissue DNA methylation profiles from the same individuals and adjusting for cell-type heterogeneity, demonstrating that a substantial amount of epigenetic drift, possibly over 70%, is shared between significant numbers of different tissue/cell types. We further show that ELOVL2 is not unique and that many other CpG sites, some mapping to genes in the Wnt and glutamate receptor signaling pathways, are altered with age across at least 10 different cell/tissue types. We propose that while most age-associated DNAm changes are shared between cell-types that the putative functional effect is likely to be tissue-specific.
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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
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Kelsey KT
影响因子：
3.7
作者：
Teschendorff AE;Menon U;Gentry-Maharaj A;Ramus SJ;Gayther SA;Apostolidou S;Jones A;Lechner M;Beck S;Jacobs IJ;Widschwendter M
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Widschwendter M
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影响因子：
12.3
作者：
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通讯作者：
Irizarry RA
全基因组甲基化谱揭示了人类衰老速度的定量观点。
影响因子：
16
作者：
Hannum, Gregory;Guinney, Justin;Zhao, Ling;Zhang, Li;Hughes, Guy;Sadda, SriniVas;Klotzle, Brandy;Bibikova, Marina;Fan, Jian-Bing;Gao, Yuan;Deconde, Rob;Chen, Menzies;Rajapakse, Indika;Friend, Stephen;Ideker, Trey;Zhang, Kang
通讯作者：
Zhang, Kang