8-Oxo-7,8 dihydroguanine (8-oxoG) accumulates in the genome over time and is believed to contribute to the development of aging characteristics of skeletal muscle and various aging-related diseases. We have investigated the accumulation and the possible role of 8-oxoG and 8-oxoguanine DNA glycosylase (OGG1) in exercise and aging models. Aging increased the accumulation of 8-oxoG in human and rat skeletal muscle as well as in rat hippocampus. A single bout of exercise increased the level of 8-oxoG, while regular exercise even with moderate level decreased the accumulation in skeletal muscles. On the other hand, exercise intervention was not effective in the brain. We have shown that OGG1 is acetylated and activated in vivo and induced by a single bout of exercise and exercise training too. Ac-OGG1 was associated with significant decrease in 8-oxoG, in general. We have checked the interaction between SIRT1, which is a potential enzyme to deacetylate OGG1, and our data suggest that SIRT1 can negatively control the excision of 8-oxoG. Then the question arises whether the age-associated decline in the activity of SIRT1 is linked to the need of the acetylation of OGG1 to enhance the activity and cope with the increased level of 8-oxoG.