Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress

Tory M. Hagen*, Jiankang Liu†,‡, Jens Lykkesfeldt§, Carol M. Wehr†, Russell T. Ingersoll‡, Vladimir Vinarsky†, James C. Bartholomew¶, and Bruce N. Ames†,‡,‖

Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331; †Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720; ‡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

Abstract
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)-α-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.

Footnotes
↵ ‖ 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@uclink4.berkeley.edu.
Abbreviations: ALCAR, acetyl-l-carnitine; LA, lipoic acid; MDA, malondialdehyde; ROS, reactive oxygen species
Copyright © 2002, The National Academy of Sciences