Zhu Tianyu, Zheng Shijie C, Paul Dirk S, Horvath Steve, Teschendorff Andrew E
CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK.
Aging (Albany NY). 2018 Nov 27;10(11):3541-3557. doi: 10.18632/aging.101666.
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.
年龄相关的DNA甲基化变化已在许多不同的组织和细胞类型中得到广泛报道。能够以惊人的高精度预测实际年龄的表观遗传“时钟”似乎独立于组织和细胞类型发挥作用，这表明表观遗传漂变的一个组成部分是细胞类型独立的。然而，特定于细胞或组织类型的年龄相关DNA甲基化变化的相对量与独立于细胞或组织类型发生的量尚不清楚，这是一个有争议的问题，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，我们进行了一项新颖的综合统计分析，包括来自同一受试者的匹配多细胞类型和多组织DNA甲基化谱，并针对细胞类型异质性进行调整，结果表明大量的表观遗传漂变（可能超过70%）在大量不同的组织/细胞类型之间是共享的。我们进一步表明，ELOVL2并非独一无二，许多其他CpG位点，其中一些映射到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/组织类型中随年龄而改变。我们提出，虽然大多数与年龄相关的DNA甲基化变化在细胞类型之间是共享的，但假定的功能效应可能是组织特异性的。
