MITOCHONDRIAL COMPLEX-I DEFECTS IN AGING

According to the 'mitochondrial theory of aging' it is expected that t he activity of NADH Coenzyme Q reductase (Complex I) would be most sev erely affected among mitochondrial enzymes, since mitochondrial DNA en codes for 7 subunits of this enzyme. Being these subunits the site of binding of the acceptor substrate (Coenzyme Q) and of most inhibitors of the enzyme, it is also expected that subtle kinetic changes of quin one affinity and enzyme inhibition could develop in aging before an ov erall loss of activity would be observed. The overall activity of Comp lex I was decreased in several tissues from aged rats, nevertheless it was found that direct assay of Complex I using artificial quinone acc epters may underevaluate the enzyme activity. The most acceptable resu lts could be obtained by applying the 'pool equation' to calculate Com plex I activity from aerobic NADH oxidation; using this method it was found that the decrease in Complex I activity in mitochondria from old animals was greater than the activity calculated by direct assay of N ADH Coenzyme Q reductase. A decrease of NADH oxidation and its rotenon e sensitivity was observed in nonsynaptic mitochondria, but not in syn aptic 'light' and 'heavy' mitochondria of brain cortex from aged rats. In a study of Complex I activity in human platelet membranes we found that the enzyme activity was unchanged but the titre for half-inhibit ion by rotenone was significantly increased in aged individuals and pr oposed this change as a suitable biomarker of aging and age-related di seases.