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RESEARCH COMMUNICATION |
-Lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA; and
a Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA
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.—Hagen, T. M., Ingersoll,
R. T., Lykkesfeldt, J., Liu, J., Wehr, C. M., Vinarsky, V.,
Bartholomew, J. C., Ames, B. N. (R)-
-Lipoic
acid-supplemented old rats have improved mitochondrial function,
decreased oxidative damage, and increased metabolic rate.
Key Words: aging • ambulatory activity • MDA • antioxidants • liver
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