title: (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate.
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.
authors.affiliation: Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Hagen
authors.forename: R T
authors.initials: RT
authors.lastname: Ingersoll
authors.forename: J
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: C M
authors.initials: CM
authors.lastname: Wehr
authors.forename: V
authors.initials: V
authors.lastname: Vinarsky
authors.forename: J C
authors.initials: JC
authors.lastname: Bartholomew
authors.forename: A B
authors.initials: AB
authors.lastname: Ames
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D004032:Diet; D019587:Dietary Supplements; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D008063:Thioctic Acid / Q000008:administration & dosage*