Aging Aging

Damage to Mitochondria 23718Causes and Consequencesof Damage to MitochondriaStudy of Functional Aspects by Flow CytometryFederico V. Pallardo, Juan Sastre, Jaime Miquel, and José Viña1. IntroductionA rapidly increasing amount of data supports the view that progressivebioenergetic loss caused by injury of the main energy-producing subcellularorganelles, that is, the mitochondria, plays a key role in aging. A link betweensenescence and energy loss is already implied in Harman’s (1) free radicaltheory of aging, according to which oxygen-derived free radicals injure thecells, with concomitant impairment of performance at the cellular and physiologicallevels. Further, Miquel and co-workers (2,3) have proposed a mitochondrialtheory of aging, according to which aging results from oxygen stressdamage to the mitochondrial genome, with concomitant bioenergetic decline.More recently, a number of laboratories, including our own (4–6), have providedbiochemical data in agreement with the above views. Thus, we haveshown that, as the result of age-related oxygen stress, mitochondrial glutathioneis oxidized in direct relation to injury of the mitochondrial DNA (5). Further,our studies suggest that an antioxidant product extracted from Ginkgo bilobamay counteract in part the damaging effects of free radicals on mitochondrialand cellular aging (7).As reviewed elsewhere (6), age-related functional changes in mitochondrialrespiration and in transport systems have been reported. Nevertheless, becauseof differences in the techniques and biological aging models used, the literatureon mitochondrial aging abounds in conflicting reports. Further, it is often difficultto assess the functional significance of the mitochondrial changes shown bystandard biochemical techniques. This makes it advisable to study the effects ofFrom: Methods in Molecular Medicine, Vol. 38: Aging Methods and ProtocolsEdited by: Y. A. Barnett and C. R. Barnett © Humana Press Inc., Totowa, NJ237