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dc.contributor.authorLangie, SAS
dc.contributor.authorCameron, KM
dc.contributor.authorFicz, G
dc.contributor.authorOxley, D
dc.contributor.authorTomaszewski, B
dc.contributor.authorGorniak, JP
dc.contributor.authorMaas, LM
dc.contributor.authorGodschalk, RWL
dc.contributor.authorvan Schooten, FJ
dc.contributor.authorReik, W
dc.contributor.authorvon Zglinicki, T
dc.contributor.authorMathers, JC
dc.identifier.citationLangie, A. S., et al. (2017). "The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice." Genes 8(2). 75 doi:10.3390/genes8020075en_US
dc.description.abstractBase excision repair (BER) may become less effective with ageing resulting in accumulation of DNA lesions, genome instability and altered gene expression that contribute to age-related degenerative diseases. The brain is particularly vulnerable to the accumulation of DNA lesions; hence, proper functioning of DNA repair mechanisms is important for neuronal survival. Although the mechanism of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events (e.g., DNA methylation) contribute to the ageing process and may be functionally important through the regulation of the expression of DNA repair genes. We hypothesize that epigenetic mechanisms are involved in mediating the age-related decline in BER in the brain. Brains from male mice were isolated at 3-32 months of age. Pyrosequencing analyses revealed significantly increased Ogg1 methylation with ageing, which correlated inversely with Ogg1 expression. The reduced Ogg1 expression correlated with enhanced expression of methyl-CpG binding protein 2 and ten-eleven translocation enzyme 2. A significant inverse correlation between Neil1 methylation at CpG-site2 and expression was also observed. BER activity was significantly reduced and associated with increased 8-oxo-7,8-dihydro-2'-deoxyguanosine levels. These data indicate that Ogg1 and Neil1 expression can be epigenetically regulated, which may mediate the effects of ageing on DNA repair in the brain.en_US
dc.description.sponsorshipThe Centre for Ageing & Vitality is funded by the MRC and BBSRC (Grant Reference MR/L016354/1). This work was further supported by the Centre for Integrated Systems Biology of Ageing and Nutrition funded by the BBSRC and EPSRC (G0700718). Part of the work was supported by BBSRC Grant BB/K010867/1.en_US
dc.relation.ispartofGenes (Basel)
dc.rightsCreative Commons Attribution License
dc.subjectDNA methylationen_US
dc.subjectbase excision repairen_US
dc.subjectgene regulationen_US
dc.titleThe Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice.en_US
dc.rights.holder2017 The Authors.
pubs.organisational-group/Queen Mary University of London
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute
pubs.organisational-group/Queen Mary University of London/Faculty of Medicine & Dentistry/Barts Cancer Institute/Haemato-Oncology
pubs.publication-statusPublished online

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