Authors
Hagen TM. Ingersoll RT. Lykkesfeldt J. Liu J. Wehr CM. Vinarsky V.
Bartholomew JC. Ames AB.
Institution
Department of Molecular and Cell Biology, University of California at
Berkeley, Berkeley, California 94720, USA.
Title
(R)-alpha-lipoic acid-supplemented old rats have improved
mitochondrial function, decreased oxidative damage, and increased metabolic
rate.
Source
FASEB Journal. 13(2):411-8, 1999 Feb.
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<0. 03) and
mitochondrial membrane potential. (R)-Lipoic acid
supplementation reversed the age-related decline in O2 consumption and
increased (P<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<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'-dichlorofluorescin, was significantly lowered in (R)-lipoic
acid supplemented old rats (P<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<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.