不同人体组织类型中与计时年龄相关的 DNA 甲基化。

IF 4.2 2区 生物学 Q1 GENETICS & HEREDITY
Niyati Jain, James L Li, Lin Tong, Farzana Jasmine, Muhammad G Kibriya, Kathryn Demanelis, Meritxell Oliva, Lin S Chen, Brandon L Pierce
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引用次数: 0

摘要

背景:虽然人们已经广泛研究了计时年龄与全血中 DNA 甲基化(DNAm)的关系,但与年龄相关的 DNAm 变化的组织特异性仍是一个活跃的研究领域。在大脑、皮肤、免疫细胞、脂肪和肝脏等组织中调查年龄与 DNAm 关联性的研究发现了组织特异性和非特异性效应,从而激发了对不同人体组织和细胞类型的更多研究:在这里,我们利用基因型-组织表达(GTEx)项目中代表 9 种组织类型(乳腺、肺、结肠、卵巢、前列腺、骨骼肌、睾丸、全血和肾脏)的 961 个组织样本的 DNAm 数据(Illumina EPIC 阵列)进行了一项全表观基因组关联研究。我们发现了与年龄相关的 CpG 位点(假发现率 结论:我们发现了与年龄相关的 CpG 位点:总之,我们的研究结果将有助于未来开发衰老生物标记物和了解不同人体组织类型的衰老机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNA methylation correlates of chronological age in diverse human tissue types.

Background: While the association of chronological age with DNA methylation (DNAm) in whole blood has been extensively studied, the tissue-specificity of age-related DNAm changes remains an active area of research. Studies investigating the association of age with DNAm in tissues such as brain, skin, immune cells, fat, and liver have identified tissue-specific and non-specific effects, thus, motivating additional studies of diverse human tissue and cell types.

Results: Here, we performed an epigenome-wide association study, leveraging DNAm data (Illumina EPIC array) from 961 tissue samples representing 9 tissue types (breast, lung, colon, ovary, prostate, skeletal muscle, testis, whole blood, and kidney) from the Genotype-Tissue Expression (GTEx) project. We identified age-associated CpG sites (false discovery rate < 0.05) in 8 tissues (all except skeletal muscle, n = 47). This included 162,002 unique hypermethylated and 90,626 hypomethylated CpG sites across all tissue types, with 130,137 (80%) hypermethylated CpGs and 74,703 (82%) hypomethylated CpG sites observed in a single tissue type. While the majority of age-associated CpG sites appeared tissue-specific, the patterns of enrichment among genomic features, such as chromatin states and CpG islands, were similar across most tissues, suggesting common mechanisms underlying cellular aging. Consistent with previous findings, we observed that hypermethylated CpG sites are enriched in regions with repressed polycomb signatures and CpG islands, while hypomethylated CpG sites preferentially occurred in non-CpG islands and enhancers. To gain insights into the functional effects of age-related DNAm changes, we assessed the correlation between DNAm and local gene expression changes to identify age-related expression quantitative trait methylation (age-eQTMs). We identified several age-eQTMs present in multiple tissue-types, including in the CDKN2A, HENMT1, and VCWE regions.

Conclusion: Overall, our findings will aid future efforts to develop biomarkers of aging and understand mechanisms of aging in diverse human tissue types.

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来源期刊
Epigenetics & Chromatin
Epigenetics & Chromatin GENETICS & HEREDITY-
CiteScore
7.00
自引率
0.00%
发文量
35
审稿时长
1 months
期刊介绍: Epigenetics & Chromatin is a peer-reviewed, open access, online journal that publishes research, and reviews, providing novel insights into epigenetic inheritance and chromatin-based interactions. The journal aims to understand how gene and chromosomal elements are regulated and their activities maintained during processes such as cell division, differentiation and environmental alteration.
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