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Age-related DNA methylation changes are tissue-specific with ELOVL2 promoter methylation as exception

Research output: Contribution to journalArticle

Original languageEnglish
Article number25
Number of pages11
JournalEpigenetics and Chromatin
Volume11
Issue number1
DOIs
DateAccepted/In press - 21 May 2018
DatePublished (current) - 30 May 2018

Abstract

Background: The well-established association of chronological age with changes in DNA methylation is primarily founded on the analysis of large sets of blood samples, while conclusions regarding tissue-specificity are typically based on small number of samples, tissues and CpGs. Here, we systematically investigate the tissue-specific character of age-related DNA methylation changes at the level of the CpG, functional genomic region and nearest gene in a large dataset. Results: We assembled a compendium of public data, encompassing genome-wide DNA methylation data (Illumina 450k array) on 8092 samples from 16 different tissues, including 7 tissues with moderate to high sample numbers (Dataset size range 96-1202, N total = 2858). In the 7 tissues (brain, buccal, liver, kidney, subcutaneous fat, monocytes and T-helper cells), we identified 7850 differentially methylated positions that gained (gain-aDMPs; cut-offs: P bonf ≤ 0.05, effect size ≥ 2%/10 years) and 4,287 that lost DNA methylation with age (loss-aDMPs), 92% of which had not previously been reported for whole blood. The majority of all aDMPs identified occurred in one tissue only (gain-aDMPs: 85.2%; loss-aDMPs: 97.4%), an effect independent of statistical power. This striking tissue-specificity extended to both the functional genomic regions (defined by chromatin state segmentation) and the nearest gene. However, aDMPs did accumulate in regions with the same functional annotation across tissues, namely polycomb-repressed CpG islands for gain-aDMPs and regions marked by active histone modifications for loss-aDMPs. Conclusion: Our analysis shows that age-related DNA methylation changes are highly tissue-specific. These results may guide the development of improved tissue-specific markers of chronological and, perhaps, biological age.

    Research areas

  • 450 k, Ageing, DNA methylation, Tissue-specific

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via BioMed Central at https://epigeneticsandchromatin.biomedcentral.com/articles/10.1186/s13072-018-0191-3 . Please refer to any applicable terms of use of the publisher.

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