Mitochondria, oxidative stress and aging
Review of research articles published in 2009 that have made or will make a significant contribution to the study of aging – Part 3.
The free radical theory, according to which the cause of aging is the accumulation of oxidative damage, was critically revised in 2009. Firstly, overexpression of the main antioxidant enzymes that reduce the amount of free radicals did not increase the lifespan of mice [16]. Secondly, the removal of the mitochondrial superoxide dismutase (Sod-2) gene increased the lifespan of Caenorhabditis elegans roundworms [17]. Thirdly, there was no correlation between the increase in the life expectancy of fruit flies associated with a low-calorie diet and the prevention of DNA damage to somatic cells [18]. Fourth, the haplon-sufficiency of the Sod-2 enzyme did not accelerate the aging of mice, even those with abnormally functioning telomeres [19]. In addition, it was demonstrated that a decrease in the level of energy metabolism and an increase in oxidative stress in the mitochondria of young mice of the Mclk1+/- line provides almost absolute protection against age-associated decrease in mitochondrial functionality. Moreover, such an altered state of mitochondria turned out to be interrelated with a significant decrease in the rate of formation of oxidative biomarkers of aging. Thus, the results of this study indicate that mitochondrial oxidative stress is not the cause of aging [20]. Data were presented according to which RNA interference of five genes encoding components of mitochondrial respiratory complexes I, III, IV and V leads to an increase in the lifespan of flies. In long-lived flies with low expression of electron transport chain genes, there is no decrease in the activity of the assembly of respiratory complexes or ATP levels. In addition, there was no correlation between an increase in life expectancy and increased resistance to the herbicide paraquat, which causes the formation of free radicals [21].
The listed results do not contradict earlier publications. This confirms that, in comparison with the effects of mutations of genes encoding components of signal transduction mechanisms, the overexpression of antioxidants has a negligible effect on increasing the lifespan of yeast, flies and mice. Apparently, in order to ensure an effective increase in life expectancy, enhanced protection against the action of superoxide should be accompanied by a number of other changes. For example, when studying the Podospora anserine fungal aging model, LON-AAA protease localized in the mitochondrial matrix increased stress resistance and oxygen consumption by mitochondria, while reducing the amount of oxidative damage to proteins [22]. Removal of the gene encoding the enzyme O-methyltransferase, which reduces the level of reactive oxygen species, from the genome of the same model organism led to an increase in life expectancy [23].
Continuation: Low-calorie diet and aging.
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