Implications of oxidative damage to proteins and DNA in aging and its intervention by caloric restriction and exercise

In this short review we describe implications of age-related changes of protein and DNA oxidation as a public mechanism of biological aging. Oxidatively modified protein and DNA have been demonstrated to increase with advancing age in rodents. Half-life of proteins is extended and DNA repair activity declines in old animals. Dietary restriction initiated late in life can shorten the half-life of proteins to levels of young animals, thus contributing to reduce level of altered proteins in old animals by the regimen. Regular exercise reduced oxidatively modified proteins in the brain with improved cognitive functions. It attenuated oxidative stress in the liver, i.e., ameliorating activation of nuclear factor κB, increasing reduced glutathione, and decreasing oxidized guanine base in nuclear and mitochondrial DNA. These findings suggest that regular exercise has systemic effects in reducing oxidative stress. Thus, life-styles such as diet and exercise may extend health span, by up-regulating overall anti-oxidant capacities that include proteins involved in protein turnover and DNA repair, resulting in reduction of damaged proteins and DNA that potentially promote physiological and pathological aging.