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UPDATING THE MITOCHONDRIAL FREE RADICAL THEORY OF AGING: AN INTEGRATED VIEW, KEY ASPECTS AND CONFOUNDING CONCEPTS.
Antioxid Redox Signal. 2013 May 5. [Epub ahead of print] doi:
Barja G
Abstract:
Abstract. An updated version of the mitochondrial free radical theory of aging and longevity is reviewed. Key aspects of the theory are emphasized. Another main focus concerns common misconceptions that can mislead investigators from other specialties even to wrongly discard the theory. Those different issues include: a) the main ROS-generating site in the respiratory chain in relation to aging and longevity: complex I; b) the close vicinity or even contact between that site and the mtDNA, in relation to the lack of local efficacy of antioxidants and to sub-cellular compartmentation; c) the relationship between mitochondrial ROS production and oxygen consumption; d) recent criticisms on the mitochondrial free radical theory of aging; e) the widespread assumption that ROS are simple "by-products" of the mitochondrial respiratory chain; f) the unnecessary postulation of "vicious cycle" hypotheses of mitochondrial ROS generation which are not central to the free radical theory of aging; e) the role of DNA repair concerning endogenous versus exogenous damage. After considering the large body of data already available two general characteristics responsible for the high maintenance degree of long-lived animals emerge: a) a low generation rate of endogenous damage: and b) the possession of tissue macromolecules highly resistant to oxidative modification.
PMID: 23642158
Tags: MFRToA