title: The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice.
abstract: Base 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 increasedOgg1methylation with ageing, which correlated inversely withOgg1expression. The reducedOgg1expression correlated with enhanced expression of methyl-CpG binding protein 2 and ten-eleven translocation enzyme 2. A significant inverse correlation betweenNeil1methylation 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 thatOgg1andNeil1expression can be epigenetically regulated, which may mediate the effects of ageing on DNA repair in the brain.
authors.affiliation: Centre for Ageing and Vitality, Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. sabine.langie@vito.be.
authors.forename: Sabine A S
authors.initials: SA
authors.lastname: Langie
authors.affiliation: The Ageing Biology Centre and Institute for Cell and Molecular Biology, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. kerry.m.cameron@effem.com.
authors.forename: Kerry M
authors.initials: KM
authors.lastname: Cameron
authors.affiliation: Barts Cancer Institute, Queen Mary University, London EC1M 6BQ, UK. g.ficz@qmul.ac.uk.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ficz
authors.affiliation: Mass Spectrometry Laboratory, Babraham Institute, Cambridge CB22 3AT, UK. david.oxley@babraham.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Oxley
authors.affiliation: Centre for Ageing and Vitality, Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. tomaszewski.bartlomiej@gmail.com.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Tomaszewski
authors.affiliation: Centre for Ageing and Vitality, Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. joanna.p.gorniak@googlemail.com.
authors.forename: Joanna P
authors.initials: JP
authors.lastname: Gorniak
authors.affiliation: Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands. l.maas@maastrichtuniversity.nl.
authors.forename: Lou M
authors.initials: LM
authors.lastname: Maas
authors.affiliation: Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands. r.godschalk@maastrichtuniversity.nl.
authors.forename: Roger W L
authors.initials: RW
authors.lastname: Godschalk
authors.affiliation: Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands. f.vanschooten@maastrichtuniversity.nl.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK. wolf.reik@babraham.ac.uk.|Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK. wolf.reik@babraham.ac.uk.
authors.forename: Wolf
authors.initials: W
authors.lastname: Reik
authors.affiliation: The Ageing Biology Centre and Institute for Cell and Molecular Biology, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. t.vonzglinicki@newcastle.ac.uk.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Zglinicki
authors.affiliation: Centre for Ageing and Vitality, Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK. john.mathers@ncl.ac.uk.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
keywords: DNA methylation; ageing; base excision repair; brain; epigenetics; gene regulation