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PNAS | February 19, 2002 | vol. 99 | no. 4 | 1870-1875
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Biochemistry
 Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress

Tory M. Hagen*, Jiankang Liudagger ,Dagger , Jens Lykkesfeldt§, Carol M. Wehrdagger , Russell T. IngersollDagger , Vladimir Vinarskydagger , James C. Bartholomew, and Bruce N. Amesdagger ,Dagger ,||

* Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331; dagger  Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; Dagger  Children's Hospital Oakland Research Institute, Oakland, CA 94609; § Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Copenhagen DK-1870, Denmark; and  Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Contributed by Bruce N. Ames, December 28, 2001

Mitochondrial-supported bioenergetics decline and oxidative stress increases during aging. To address whether the dietary addition of acetyl-L-carnitine [ALCAR, 1.5% (wt/vol) in the drinking water] and/or (R)-alpha -lipoic acid [LA, 0.5% (wt/wt) in the chow] improved these endpoints, young (2-4 mo) and old (24-28 mo) F344 rats were supplemented for up to 1 mo before death and hepatocyte isolation. ALCAR+LA partially reversed the age-related decline in average mitochondrial membrane potential and significantly increased (P = 0.02) hepatocellular O2 consumption, indicating that mitochondrial-supported cellular metabolism was markedly improved by this feeding regimen. ALCAR+LA also increased ambulatory activity in both young and old rats; moreover, the improvement was significantly greater (P = 0.03) in old versus young animals and also greater when compared with old rats fed ALCAR or LA alone. To determine whether ALCAR+LA also affected indices of oxidative stress, ascorbic acid and markers of lipid peroxidation (malondialdehyde) were monitored. The hepatocellular ascorbate level markedly declined with age (P = 0.003) but was restored to the level seen in young rats when ALCAR+LA was given. The level of malondialdehyde, which was significantly higher (P = 0.0001) in old versus young rats, also declined after ALCAR+LA supplementation and was not significantly different from that of young unsupplemented rats. Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone.

|| To whom reprint requests should be addressed at: Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr., Way, Oakland, CA 94609. E-mail: bnames{at}uclink4.berkeley.edu.

www.pnas.org/cgi/doi/10.1073/pnas.261708898
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