Oxidative Damage

Oxidative damage

Accumulation of oxidative damage may lead to cognitive dysfunction.

In aerobic organisms the energy needed to fuel biological functions is produced in the mitochondria via the electron transport chain. In addition to energy, reactive oxygen species (ROS) are produced which have the potential to cause cellular damage. ROS can damage DNA, RNA, and proteins which theoretically contributes to the physiology of ageing.
ROS are produced as a normal product of cellular metabolism. In particular, one major contributor to oxidative damage is hydrogen peroxide (H₂O₂) which is converted from superoxide that leaks from the mitochondria. Within the cell there is catalase and superoxide dismutase that help to minimize the damaging effects of hydrogen peroxide by converting it into oxygen and water, benign molecules, however this conversion is not 100% efficient, and residual peroxides persist in the cell. While ROS are produced as a product of normal cellular functioning, excessive amounts can cause deleterious effects.^[1] Memory capabilities decline with age, evident in human degenerative diseases such as Alzheimer’s disease which is accompanied by an accumulation of oxidative damage. Current studies demonstrate that the accumulation of ROS can decrease an organism’s fitness because oxidative damage is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction as demonstrated in a study where old rats were given Protandim and then given cognitive tests, results showed that the rats performed better after receiving the metabolites, suggesting that the metabolites reduced oxidative damage and improved mitochondrial function.^[2] Accumulating oxidative damage can then affect the efficiency of mitochondria and further increase the rate of ROS production.^[3] The accumulation of oxidative damage and its implications for aging depends on the particular tissue type where the damage is occurring. Additional experimental results suggest that oxidative damage is responsible for age related decline in brain functioning. Older gerbils were found to have higher levels of oxidized protein in comparison to younger gerbils. When old and young mice were treated with a spin trapping compound the level of oxidized proteins decreased in older gerbils but did not have an effect on younger gerbils. Additionally, older gerbils performed cognitive tasks better during treatment but ceased functional capacity when treatment was discontinued causing oxidized protein levels to increase. This lead researchers to conclude that oxidation of cellular proteins is potentially important for brain function .

Carney