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Cell and tissue type independent age-associated DNA methylation changes are not rare but common.

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cam.issuedOnline2018-11-27
dc.contributor.authorZhu, Tianyu
dc.contributor.authorZheng, Shijie C
dc.contributor.authorPaul, Dirk S
dc.contributor.authorHorvath, Steve
dc.contributor.authorTeschendorff, Andrew E
dc.contributor.orcidPaul, Dirk [0000-0002-8230-0116]
dc.date.accessioned2018-12-18T00:30:13Z
dc.date.available2018-12-18T00:30:13Z
dc.date.issued2018-11-27
dc.description.abstractAge-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.
dc.format.mediumPrint
dc.identifier.doi10.17863/CAM.34322
dc.identifier.eissn1945-4589
dc.identifier.issn1945-4589
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287012
dc.languageeng
dc.language.isoeng
dc.publisherImpact Journals, LLC
dc.publisher.urlhttp://dx.doi.org/10.18632/aging.101666
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectDNA methylation
dc.subjectepigenetic clock
dc.subjectepigenetic drift
dc.subjectAging
dc.subjectBrain
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectCervix Uteri
dc.subjectCheek
dc.subjectDNA Methylation
dc.subjectEpigenesis, Genetic
dc.subjectFemale
dc.subjectFibroblasts
dc.subjectHumans
dc.subjectLiver
dc.subjectMale
dc.titleCell and tissue type independent age-associated DNA methylation changes are not rare but common.
dc.typeArticle
dcterms.dateAccepted2018-11-15
prism.endingPage3557
prism.issueIdentifier11
prism.publicationDate2018
prism.publicationNameAging (Albany NY)
prism.startingPage3541
prism.volume10
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
rioxxterms.licenseref.startdate2018-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.18632/aging.101666

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