Evidence
Numerous studies have demonstrated a role for free radicals in the aging process and thus tentatively support the free radical theory of aging. Studies have shown a significant increase in superoxide radical (SOR) formation and lipid peroxidation in aging rats. Chung et al. suggest ROS production increases with age and indicated the conversion of XDH to XOD may be an important contributing factor. This was supported by a study that showed superoxide production by xanthine oxidase and NO synthase in mesenteric arteries was higher in older rats than young ones.
Hamilton et al. examined the similarities in impaired endothelial function in hypertension and aging in humans and found a significant overproduction of superoxide in both. This finding is supported by a 2007 study which found that endothelial oxidative stress develops with aging in healthy men and is related to reductions in endothelium-dependant dilation. Furthermore, a study using cultured smooth muscle cells displayed increased reactive oxygen species (ROS) in cells derived from older mice. These findings were supported by a second study using Leydig cells isolated from the testes of young and old rats.
The Choksi et al. experiment with Ames dwarf (DW) mice suggests the lower levels of endogenous ROS production in DW mice may be a factor in their resistance to oxidative stress and long life. Lener et al. suggest Nox4 activity increases oxidative damage in human umbilical vein endothelial cells via superoxide overproduction. Furthermore, Rodriguez-Manas et al. found endothelial dysfunction in human vessels is due to the collective effect of vascular inflammation and oxidative stress.
Sasaki et al. reported superoxide-dependent chemiluminescence was inversely proportionate to maximum lifespan in mice, Wistar rats, and pigeons. They suggest ROS signalling may be a determinant in the aging process. Mendoza-Nunez et al. propose an age of 60 years or older may be linked with increased oxidative stress. Miyazawa found mitochondrial superoxide anion production can lead to organ atrophy and dysfunction via mitochondrial- mediated apoptosis. In addition, they suggest mitochondrial superoxide anion plays an essential part in aging. Lund et al. demonstrated the role of endogenous extracellular superoxide dismutase in protecting against endothelial dysfunction during the aging process using mice.
Read more about this topic: Free-radical Theory Of Aging
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