Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.

By Vardhman K. Rakyan, Thomas A. Down, Siarhei Maslau, T. Andrew, Tsun-Po Yang, H. Beyan, P. Whittaker, O. Mccann, S. Finer, A. Valdes and 3 more. Genome Research, 2010

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There is a growing realization that some aging-associated phenotypes/diseases have an epigenetic basis. Here, we report the first genome-scale study of epigenomic dynamics during normal human aging. We identify aging-associated differentially methylated regions (aDMRs) in whole blood in a discovery cohort, and then replicate these aDMRs in sorted CD4(+) T-cells and CD14(+) monocytes in an independent cohort, suggesting that aDMRs occur in precursor haematopoietic cells. Further replication of the aDMRs in buccal cells, representing a tissue that originates from a different germ layer compared with blood, demonstrates that the aDMR signature is a multitissue phenomenon. Moreover, we demonstrate that aging-associated DNA hypermethylation occurs predominantly at bivalent chromatin domain promoters. This same category of promoters, associated with key developmental genes, is frequently hypermethylated in cancers and in vitro cell culture, pointing to a novel mechanistic link between aberrant hypermethylation in cancer, aging, and cell culture.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/902aca09c76d770c7f7a34cdcad3bb42455a3146

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Citations in the corpus

A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue (2013, neutral): “%) with three studies reporting aging-differentially methylated regions (a-DMRs) in a total of 597 unique positions [28–30].”
Accounting for cellular heterogeneity is critical in epigenome-wide association studies (2014, methodology): “papers reporting age-related changes of DNAm profiles have been published [6-14].”
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease (2016, background): “Measures incorporating DNA methylation levels have recently given rise to a new class of biomarkers that appear informative of aging given that age has a profound effect on DNA methylation levels in most human tissues and cell types [10–18].”
An epigenetic biomarker of aging for lifespan and healthspan (2018, background): “Chronological time has been shown to elicit predictable hypo- and hyper-methylation changes at many regions across the genome [3-7], and as a result, the first generation of DNAm based biomarkers of aging were developed to predict chronological chronological age [8-13].”
A User's Guide to the Encyclopedia of DNA Elements (ENCODE) (2011, methodology): “…which enables quantitative analysis of methylcytosines: interrogation of the methylation status of 27,000 CpGs with the Illumina Methyl27 assay [69–72] and Reduced Representation Bisulfite Sequencing (RRBS) [73], which couples Msp I restriction enzyme digestion, size selection, bisulfite…”
Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling (2016, background): “HM27 allowed researchers to explore the role of DNA methylation in carcinogenesis and identify cancer biomarkers [9] and for the first time perform largescale ‘epigenome-wide association studies’ (EWAS), which revealed the associations between DNA methylation patterns and tobacco smoking [10], agein”
Epigenetics and the environment: emerging patterns and implications (2012, background): “Studies on ageing indicate that epigenetic variation over time preferentially occurs at specific loc”
Epigenome-Wide Scans Identify Differentially Methylated Regions for Age and Age-Related Phenotypes in a Healthy Ageing Population (2012, methodology): “hyper-methylated a-DMRs in a subset of these data (93 individuals from [14]).”
DNA methylation and healthy human aging (2015, background): “islands, while nonislands tend to lose DNA methylation with age (Rakyan et al., 2010; Heyn et al., 2012; Horvath et al., 2012; Florath et al., 2014; Weidner et al., 2014).”
DNA methylation age of human tissues and cell types (2013, background): “Commons Attribution License (http://creativec reproduction in any medium, provided the or with key developmental genes [15], and at Polycomb-group protein targets [10].”
Distinct DNA methylomes of newborns and centenarians (2012, methodology): “The platform is an extension of other DNA methylation microarrays, such as those for 1,500 CpG (30–33) and 27,000 CpG (34, 35) sites, which have been used to characterize age-related DNA methylation changes (32–36).”
Epigenetic Predictor of Age (2011, methodology): “Its methylation status was recently shown to be correlated with age in blood as well [8].”
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors (2017, neutral): “Chronological age has been shown to have a profound effect on DNA methylation levels [26-34].”
Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates (2012, positive): “In this regard, this study is consistent with a prior analysis of purified CD4+ T cells and CD14+ monocytes, in which the age-associated epigenetic modifications were found to be similar to the changes observed in whole blood (Rakyan et al., 2010).”