DNA repair systems such as 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 cellular and tissue dysfunction and increase the risk of age-related degenerative diseases. The brain is particularly vulnerable to accumulation of oxidative DNA lesions and proper functioning of DNA repair mechanisms is thus important for neuronal survival. Although the mechanism(s) of age-related decline in DNA repair capacity is unknown, growing evidence suggests that epigenetic events, including aberrant DNA methylation, contribute to the ageing process and may be functionally important through dysreguledexpression of DNA repair genes. We hypothesise that oxidative stress modulates DNA repair, specifically BER, in the ageing brain and that epigenetic mechanisms are involved in mediating age-related effects. Brains from C57/BL male mice were isolated at 3-32 months of age. Using pyrosequencing, we observed significantly increased methylation of the promoter region of the BER gene Ogg1 with ageing, which correlated inversely with Ogg1 expression. The reduced Ogg1 expression correlated with enhanced expression of methyl-CpG binding protein 2 (MeCP2) and of ten-eleven translocation enzyme 2 (Tet2). The functional consequence, if any, of the latter association is unclear since Tet enzymes can convert 5-methylcytosine to 5-hydroxy-methylcytosine and play a role in further active DNA demethylation. On this basis, one would have anticipated an inverse correlation between expression of Ogg1 and of Tet2. MeCP2 is a methyl-CpG binding protein that can suppress transcription. In adult brain, MeCP2 binds to methylated DNA across the genome and plays a crucial role in normal brain functioning. We also observed a significant inverse correlation between gene methylation and expression observed for Neil1, which is another BER gene. During ageing, there was a trend towards decreased expression of Mutyh and Xrcc1, in parallel to slightly higher gene methylation levels. The corresponding phenotype i.e. BER-related incision activity in brain was reduced significantly, which was associated with significantly increased 8-oxo-7,8-dihydro-2′-deoxyguanosine levels. These data indicate that Ogg1 and Neil1 expression can be epigenetically regulated and that this may play a role in the adverse effects of ageing on DNA repair in mammalian brain. In conclusion, this study has provide evidence that through altered expression of BER genes, epigenetic mechanisms – i.e. increased promoter methylation as well as the involvement of TET enzymes and MeCP2 – can reduce capacity for neuronal DNA repair during ageing. This reduced capacity for DNA repair may contribute to the accumulation of oxidative DNA damage and mutations across the whole genome, causing genome instability and increasing the risk of age-related neurodegenerative diseases.