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Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-l-carnitine

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Abstract

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.

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Acknowledgements

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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Authors and Affiliations

  1. Institute for Brain Aging and Dementia, University of California, Irvine, CA, 92697-4540, USA

    Jiangang Long, Liqi Tong, Carl W. Cotman & Jiankang Liu

  2. Children’s Hospital Oakland Research Institute, Oakland, CA, 94609, USA

    Jiangang Long, Feng Gao & Bruce N. Ames

  3. Graduate Center for Toxicology, University of Kentucky College of Medicine, 236 Boromworth Health Sciences Research Building, Lexington, KY, 40536, USA

    Jiankang Liu

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  1. Jiangang Long
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Correspondence to Jiankang Liu.

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Special issue article in honor of Dr. Akitane Mori.

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Long, J., Gao, F., Tong, L. et al. Mitochondrial Decay in the Brains of Old Rats: Ameliorating Effect of Alpha-Lipoic Acid and Acetyl-l-carnitine. Neurochem Res 34, 755–763 (2009). https://doi.org/10.1007/s11064-008-9850-2

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