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Genes 2017, 8(2), 75; doi:10.3390/genes8020075

The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice

1
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
2
The Ageing Biology Centre and Institute for Cell and Molecular Biology, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5PL, UK
3
Barts Cancer Institute, Queen Mary University, London EC1M 6BQ, UK
4
Mass Spectrometry Laboratory, Babraham Institute, Cambridge CB22 3AT, UK
5
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, 6200 MD Maastricht, The Netherlands
6
Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK
7
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Dennis R. Grayson
Received: 4 November 2016 / Revised: 2 February 2017 / Accepted: 7 February 2017 / Published: 17 February 2017
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
View Full-Text   |   Download PDF [2156 KB, uploaded 17 February 2017]   |  

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 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. View Full-Text
Keywords: DNA methylation; epigenetics; base excision repair; ageing; brain; gene regulation DNA methylation; epigenetics; base excision repair; ageing; brain; gene regulation
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MDPI and ACS Style

Langie, S.A.S.; Cameron, K.M.; Ficz, G.; Oxley, D.; Tomaszewski, B.; Gorniak, J.P.; Maas, L.M.; Godschalk, R.W.L.; van Schooten, F.J.; Reik, W.; von Zglinicki, T.; Mathers, J.C. The Ageing Brain: Effects on DNA Repair and DNA Methylation in Mice. Genes 2017, 8, 75.

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