Role of Oxidative DNA Damage and Antioxidative Enzymatic Defence Systems in Human Aging

ABSTRACT

Oxidative stress is regarded as a main causal factor for natural aging. This study tested the hypothesis that healthy elderly people show higher oxidative DNA damage levels and lower antioxidative enzymatic defense capacities than younger ones. In a cross-sectional study, blood samples of 20 older (62-79 years) and 20 younger adults (24-28 years) were compared with respect to oxidative DNA damage in lymphocytes (alkaline elution), oxidative status (serum peroxides), activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and concentrations of total glutathione. In accordance with our hypothesis, elderly males showed a tendency towards higher levels of oxidative DNA damage (single strand breaks). SOD activity inversely correlated with the amount of DNA damage (single-strand breaks and Fpg-sensitive modifications). Oxidative status was increased in older men and negatively correlated with glutathione concentrations. GPx activity was elevated and the SOD/GPx ratio lowered in older males. Subjects with lowered SOD/GPx ratio showed increased oxidative DNA damage. The results indicate age-related changes in the balance between first step (SOD) and second step (GPx) of the enzymatic antioxidant defense system. They support the assumption that a biological optimum between antioxidative enzymes might be more important than their absolute activities.

Keywords:

Aging, oxidative DNA damage, oxidative status, antioxidative enzymes, superoxide dismutase, glutathione per-oxidase, glutathione.