Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-l-carnitine
To investigate the mitochondrial decay and oxidative damage resulting from aging, the activities/kinetics of the mitochondrial complexes were examined in the brains of young and old rats as well as in old rats fed R-α-lipoic acid plus acetyl-l-carnitine (LA/ALC). The brain mitochondria of old rats, compared with young rats, had significantly decreased endogenous antioxidants and superoxide dismutase activity; more oxidative damage to lipids and proteins; and decreased activities of complex I, IV and V. Complex I showed a decrease in binding affinity (increase in Km) for substrates. Feeding LA/ALC to old rats partially restored age-associated mitochondrial dysfunction to the levels of the young rats. These results indicate that oxidative mitochondrial decay plays an important role in brain aging and that a combination of nutrients targeting mitochondria, such as LA/ALC, could ameliorate mitochondrial decay through preventing mitochondrial oxidative damage.
KeywordsBinding affinity (Km) Brain mitochondria Mitochondrial complex activity Enzyme kinetics Oxidative damage
The authors thank Dr. Afshin Gharib for taking care of the animals. This work was supported by the Ellison Medical Foundation Grants S-0422-99, the National Institute on Aging AG17140, and the National Center for Complementary and Alternative Medicine Research Scientist Award K05 AT001323-4 (B. N. A.), and National Institutes of Health grants NEI EY016101, NIA AG023265, and NCCAM AT01918 (B. N. A. and J. L.) and NIA AG012694 (C. W. C).
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