OXIDATIVE DAMAGE DURING AGING TARGETS MITOCHONDRIAL ACONITASE

The mechanisms that cause aging are not well understood, The oxidative stress hypothesis proposes that the changes associated with aging are a consequence of random oxidative damage to biomolecules. We hypothes ized that oxidation of specific proteins is critical in controlling th e rate of the aging process, Utilizing an immunochemical probe for oxi datively modified proteins, we show that mitochondrial aconitase, an e nzyme in the citric acid cycle, is a specific target during aging of t he housefly, The oxidative damage detected immunochemically was parall eled by a loss of catalytic activity of aconitase, an enzyme activity that is critical in energy metabolism. Experimental manipulations whic h decrease aconitase activity should therefore cause a decrease in lif e-span, This expected decrease was observed when flies were exposed to hyperoxia, which oxidizes aconitase, and when they were given fluoroa cetate, an inhibitor of aconitase, The identification of a specific ta rget of oxidative damage during aging allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.