Protein oxidation and ageing

Organisms produce reactive oxygen species (ROS) throughout their lives. The activities of a number of key antioxidant enzymes, such as catalase, superoxide dismutase and glutathione peroxidase, which protect against the damaging effects of ROS, have been reported to decrease with increasing age, though this is not unequivocal. In contrast, sacrificial antioxidants such as ascorbate, thiols and tocopherol do not appear to decrease with increasing age. It is also possible that ROS production increases with age as a result of poorer coupling of electron transport components, and an increased level of redox-active metal ions that could catalyse oxidant formation. As a result of this decrease in antioxidant defences, and increased rate of ROS formation, it is possible that the impact of ROS increases with age. ROS are known to oxidise biological macromolecules, with proteins an important target. If the argument that the impact of ROS increases with age is true, then proteins would be expected to accumulate oxidised materials with age, and the rate of such accumulation should increase with time, reflecting impaired inefficiency of homeostasis. Here we review the evidence for the accumulation of oxidised, or modified, extra- and intra-cellular proteins in vivo.