Aging and the Accumulation of Oxidative Damage to DNA

The oxidative stress hypothesis of aging is currently one of the most popular explanations for the cause of aging. Oxidative stress, including that due to reactive oxygen species, causes lesions to biomolecules such as DNA, protein and lipids. 8-Oxo-2'-deoxyguanosine (8-oxodG) is a major oxidative product of DNA and can be detected using avariety of assay methods. For an accurate measurement of 8-oxodG, it is important to minimize as much as possible the oxidation of intact DNA during its isolation from cells or tissues and during the hydrolysis of DNA to nucleosides. The most popular analyticaltechnique is high-performance liquid chromatography with electrochemical detection. The levels of oxidative damage to DNA are likely to increase in mammalian tissues during aging, although it is not clear whether the levels increase linearly during aging or exponentially in aged animals. The accumulation of oxidative damage to DNA is recognized asinducing mutations and dysfunction during aging. The steady state levels of oxidative damage to DNA are proposed to depend on the balance between the formation and repair of damage. The repair activity appears to be weak in aged animals compared with young animals, but antioxidative activity has not been shown to undergo a consistent changing pattern.Thus, it is assumed that the decline in repair activity in aged animals leads to the accumulation of oxidative damage in aged tissues.