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dc.contributor.authorLowe, Robert
dc.contributor.authorBarton, Carl
dc.contributor.authorJenkins, Christopher
dc.contributor.authorErnst, Christina
dc.contributor.authorForman, Oliver
dc.contributor.authorTwinn, Denise
dc.contributor.authorBock, Christoph
dc.contributor.authorRossiter, Stephen J
dc.contributor.authorFaulkes, Chris G
dc.contributor.authorOzanne, Susan
dc.contributor.authorWalter, Lutz
dc.contributor.authorOdom, Duncan
dc.contributor.authorMellersh, Cathryn
dc.contributor.authorRakyan, Vardhman K
dc.date.accessioned2018-04-26T13:43:41Z
dc.date.accessioned2018-06-15T15:25:59Z
dc.date.available2018-04-26T13:43:41Z
dc.date.available2018-06-15T15:25:59Z
dc.date.issued2018-02-16
dc.identifier.issn1474-7596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277126
dc.description.abstractBACKGROUND: Mammalian species exhibit a wide range of lifespans. To date, a robust and dynamic molecular readout of these lifespan differences has not yet been identified. Recent studies have established the existence of ageing-associated differentially methylated positions (aDMPs) in human and mouse. These are CpG sites at which DNA methylation dynamics show significant correlations with age. We hypothesise that aDMPs are pan-mammalian and are a dynamic molecular readout of lifespan variation among different mammalian species. RESULTS: A large-scale integrated analysis of aDMPs in six different mammals reveals a strong negative relationship between rate of change of methylation levels at aDMPs and lifespan. This relationship also holds when comparing two different dog breeds with known differences in lifespans. In an ageing cohort of aneuploid mice carrying a complete copy of human chromosome 21, aDMPs accumulate far more rapidly than is seen in human tissues, revealing that DNA methylation at aDMP sites is largely shaped by the nuclear trans-environment and represents a robust molecular readout of the ageing cellular milieu. CONCLUSIONS: Overall, we define the first dynamic molecular readout of lifespan differences among mammalian species and propose that aDMPs will be an invaluable molecular tool for future evolutionary and mechanistic studies aimed at understanding the biological factors that determine lifespan in mammals.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.relation.replaceshttps://www.repository.cam.ac.uk/handle/1810/275204
dc.relation.replaces1810/275204
dc.relation.replaces1810/275623
dc.relation.replaceshttps://www.repository.cam.ac.uk/handle/1810/275623
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAnimals
dc.subjectMammals
dc.subjectDogs
dc.subjectHumans
dc.subjectMice
dc.subjectDNA Methylation
dc.subjectAging
dc.subjectLongevity
dc.titleAgeing-associated DNA methylation dynamics are a molecular readout of lifespan variation among mammalian species.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameGenome Biol
prism.startingPage22
prism.volume19
dc.identifier.doi10.17863/CAM.22382
dc.identifier.doi10.17863/CAM.24418
dc.identifier.doi10.17863/CAM.24418
dcterms.dateAccepted2018-01-19
rioxxterms.versionofrecord10.1186/s13059-018-1397-1
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.licenseref.startdate2018-02-16
dc.contributor.orcidJenkins, Christopher [0000-0001-9082-4270]
dc.contributor.orcidErnst, Christina [0000-0002-3569-2209]
dc.contributor.orcidTwinn, Denise [0000-0003-2610-277X]
dc.contributor.orcidOzanne, Susan [0000-0001-8753-5144]
dc.contributor.orcidOdom, Duncan [0000-0001-6201-5599]
dc.contributor.orcidMellersh, Cathryn [0000-0002-2336-0370]
dc.identifier.eissn1474-760X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_12012/4)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idWellcome Trust (202878/Z/16/Z)
pubs.funder-project-idEuropean Research Council (615584)
pubs.funder-project-idBritish Heart Foundation (RG/17/12/33167)
pubs.funder-project-idCancer Research UK (20412)
pubs.funder-project-idMRC (MC_UU_00014/4)
cam.issuedOnline2018-02-16
cam.orpheus.successThu Jan 30 12:59:04 GMT 2020 - The item has an open VoR version.
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International