Free-radical theory of aging
[4] Denham Harman first proposed the free radical theory of aging in the 1950s,[5] and in the 1970s extended the idea to implicate mitochondrial production of ROS.
[8] Similarly, in roundworms (Caenorhabditis elegans), blocking the production of the naturally occurring antioxidant superoxide dismutase has been shown to increase lifespan.
[11] Free radical damage within cells has been linked to a range of disorders including cancer, arthritis, atherosclerosis, Alzheimer's disease, and diabetes.
[13] There has been some evidence to suggest that free radicals and some reactive nitrogen species trigger and increase cell death mechanisms within the body such as apoptosis and in extreme cases necrosis.
[11] In its current form, this theory proposes that reactive oxygen species (ROS) that are produced in the mitochondria, causes damage to certain macromolecules including lipids, proteins and most importantly mitochondrial DNA.
[15] This damage then causes mutations which lead to an increase of ROS production and greatly enhance the accumulation of free radicals within cells.
[22] Free radicals can oxidize LDL, and this is a key event in the formation of plaque in arteries, leading to heart disease and stroke.
Thus a positive feedback loop of oxidative stress is established that, over time, can lead to the deterioration of cells and later organs and the entire body.
[32] Afanas'ev suggests the superoxide dismutation activity of CuZnSOD demonstrates an important link between life span and free radicals.
[36] Brewer's theory suggests "sedentary behaviour associated with age triggers an oxidized redox shift and impaired mitochondrial function".
[36] The metabolic stability theory of aging suggests it is the cells ability to maintain stable concentration of ROS which is the primary determinant of lifespan.
[37] Oxidative stress may promote life expectancy of Caenorhabditis elegans by inducing a secondary response to initially increased levels of ROS.
ROS production in heart, skeletal muscle, liver and intact erythrocytes was found to be similar in parrots and quail and showed no correspondence with longevity difference.
