???Mild??? mitochondrial uncoupling as potentially effective intervention to slow aging

Abstract

Vladimir Illich Padalko

The main objective of this review is to elucidate the role of endogenous reactive oxygen species (primarily mitochondrial origin) in the aging process. We have attempted to highlight the findings from several investigations about the relationship between reduction in mitochondrial production of free radicals (using specific antioxidants or “mild” mitochondrial uncoupling) and life span. Several studies on animal models have shown that aging rates and life expectancy could be modified using mitochondria-targeted antioxidants and uncouplers. In particular, different uncoupling strategies were able to extend life span in models ranging from yeast to mammals. These findings are in line with the “uncoupling to survive” hypothesis, suggesting that uncoupling could be an approach to promote life span extension due to its ability to prevent the formation of reactive oxygen species. Obviously, because of the high toxicity, 2,4-dinitrophenol and other uncouplers themselves can not be applied in practical geriatrics, but their low toxic analogues having controlled and “soft” action either agonists affecting the natural way of uncoupling (uncoupling proteins, UCPs) are promising for the development of means for control of tissue redox state and animal life span.