( <i>R</i> )‐α‐Lipoic acid‐supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate

Abstract

ABSTRACT A diet supplemented with ( R )‐lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metabolism seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AIN‐93M diet with or without ( R )‐lipoic acid (0.5% w/w) for 2 wk, killed, and their liver parenchymal cells were isolated. Hepatocytes from untreated old rats vs. young controls had significantly lower oxygen consumption ( P &lt;0.03) and mitochondrial membrane potential. ( R )‐Lipoic acid supplementation reversed the age‐related decline in O 2 consumption and increased ( P &lt;0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rats vs. controls, but this decline was reversed ( P &lt; 0.005) in old rats fed ( R )‐lipoic acid. The increase of oxidants with age, as measured by the fluorescence produced on oxidizing 2′,7′‐dichlorofluo‐rescin, was significantly lowered in ( R )‐lipoic acid supplemented old rats ( P &lt;0.01). Malondialdehyde (MDA) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats the ( R )‐lipoic acid diet reduced MDA levels markedly ( P &lt;0.01). Both glutathione and ascorbic acid levels declined in hepatocytes with age, but their loss was completely reversed with ( R )‐lipoic acid supplementation. Thus, ( R )‐lipoic acid supplementation improves indices of metabolic activity as well as lowers oxidative stress and damage evident in aging.—Hagen, T. M., Ingersoll, R. T., Lykkesfeldt, J., Liu, J., Wehr, C. M., Vinarsky, V., Bartholomew, J. C., Ames, B. N. ( R )‐α‐Lipoic acid‐supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J. 13, 411–418 (1999)