Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.
Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle.
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DOI：
10.1002/jcsm.12741
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Eynon N
中科院分区：
文献类型：
--
作者：
Voisin S;Jacques M;Landen S;Harvey NR;Haupt LM;Griffiths LR;Gancheva S;Ouni M;Jähnert M;Ashton KJ;Coffey VG;Thompson JM;Doering TM;Gabory A;Junien C;Caiazzo R;Verkindt H;Raverdy V;Pattou F;Froguel P;Craig JM;Blocquiaux S;Thomis M;Sharples AP;Schürmann A;Roden M;Horvath S;Eynon N
骨骼肌中与年龄相关的DNA甲基化变化的知识有限，然而这种组织在人类中受到衰老的严重影响。我们进行了一项大规模的全表观基因组关联研究，荟萃分析了10项研究中人类骨骼肌的年龄（来自18-89岁男性和女性的总共908个肌肉甲基化组）。我们探索了年龄相关的染色质状态、CpG岛和转录因子结合位点的DNA甲基化变化的基因组背景，并进行了基因集富集分析。然后，我们将DNA甲基化数据与骨骼肌中已知的转录组学和蛋白质组学年龄相关的变化结合起来。最后，我们更新了我们最近开发的肌肉表观遗传时钟（https://bioconductor.org/packages/release/bioc/html/MEAT.html）。我们以严格的错误发现率<0.005确定了6710个差异甲基化区域，涵盖6367个独特基因，其中许多与骨骼肌结构和发育有关。我们发现Polycomb靶基因和二价染色质结构域的DNA甲基化显著增加，同时增强子的DNA甲基化减少。大多数差异甲基化基因在mRNA或蛋白质水平上没有改变，但对于显示年龄相关的差异mRNA和蛋白质表达的基因，它们仍然被强烈富集。在添加了来自5个数据集（+371）的大量样本后，更新版本的肌肉时钟（MEAT 2.0，总n = 1053个样本）的表现与原始版本的肌肉时钟相似（年龄预测误差的中位数为4.4岁对4.6岁），这表明原始版本的肌肉时钟非常准确。我们在这里提供了人类骨骼肌中DNA甲基化老化的最全面的图片，并揭示了骨骼肌结构、发育和分化中涉及的基因的广泛改变。我们已经将我们的结果作为一个开放获取的、用户友好的、基于web的工具MetaMeth （https://sarah‐voisin.shinyapps.io/MetaMeth/）。
Knowledge of age‐related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans. We conducted a large‐scale epigenome‐wide association study meta‐analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18–89 years old). We explored the genomic context of age‐related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis. We then integrated the DNA methylation data with known transcriptomic and proteomic age‐related changes in skeletal muscle. Finally, we updated our recently developed muscle epigenetic clock (https://bioconductor.org/packages/release/bioc/html/MEAT.html). We identified 6710 differentially methylated regions at a stringent false discovery rate <0.005, spanning 6367 unique genes, many of which related to skeletal muscle structure and development. We found a strong increase in DNA methylation at Polycomb target genes and bivalent chromatin domains and a concomitant decrease in DNA methylation at enhancers. Most differentially methylated genes were not altered at the mRNA or protein level, but they were nonetheless strongly enriched for genes showing age‐related differential mRNA and protein expression. After adding a substantial number of samples from five datasets (+371), the updated version of the muscle clock (MEAT 2.0, total n = 1053 samples) performed similarly to the original version of the muscle clock (median of 4.4 vs. 4.6 years in age prediction error), suggesting that the original version of the muscle clock was very accurate. We provide here the most comprehensive picture of DNA methylation ageing in human skeletal muscle and reveal widespread alterations of genes involved in skeletal muscle structure, development, and differentiation. We have made our results available as an open‐access, user‐friendly, web‐based tool called MetaMeth (https://sarah‐voisin.shinyapps.io/MetaMeth/).
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
168.9
作者：
Dick, Katherine J.;Nelson, Christopher P.;Samani, Nilesh J.
通讯作者：
Samani, Nilesh J.
与年龄和疾病相关的肌肉损失：糖尿病、肥胖和其他疾病的影响。
影响因子：
44.5
作者：
Kalyani, Rita Rastogi;Corriere, Mark;Ferrucci, Luigi
通讯作者：
Ferrucci, Luigi
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
DOI：
10.1038/nrrheum.2017.60
发表时间：
2017-06
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Dennison EM;Sayer AA;Cooper C
通讯作者：
Cooper C