Mitochondrial oxidative stress. Physiologic consequences and potential for a role in aging.
During the last 10 years, the theory known as the "free radical theory of aging" has achieved prominence as one of the most compelling explanations for many of the degenerative changes associated with aging. Although its appeal derives from a long-standing body of supporting correlative data, the theory was only recently more rigorously tested. Ongoing researches in the study of free radical biochemistry and the genetics of aging have been at the forefront of this work. First, transgenic approaches in invertebrate models with candidate genes such as superoxide dismutase (SOD) involved in the detoxification of reactive oxygen species (ROS) have shown that the endogenous production of ROS due to normal physiologic processes is a major limiter of life span. Genes involved in ROS detoxification are highly conserved among eukaryotes; hence, the physiologic processes that limit life span in invertebrates are likely to be similar in higher eukaryotes. Secondly, transgenic mice deficient in the antioxidant enzyme mitochondrial superoxide dismutase (SOD2) die within their first week of life, demonstrating the importance of limiting endogenous mitochondrial free radicals in mammals. Together, data from studies using transgenic invertebrates and those using sod2 mutant mice demonstrate that modulation of metabolic ROS can have a profound effect on life span. We show here that the effects of mitochondrial ROS can be modulated through appropriate catalytic antioxidant intervention. These catalytic antioxidants are discussed in the context of mitochondrial oxidative stress and their potential role in intervening in mitochondrial oxidative stress and aging.
Melov
S
S
Buck Center for Research in Aging, Novato, California 94948-0638, USA. smelov@buckcenter.org
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002384:Catalysis; D008017:Life Expectancy; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics
D000975:Antioxidants; D013482:Superoxide Dismutase