(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate

A diet supplemented with (R)-lipoic acid, a mitochondrial coenzyme, was fed to old rats to determine its efficacy in reversing the decline in metaboli sm seen with age. Young (3 to 5 months) and old (24 to 26 months) rats were fed an AlN-93M diet with or without (R)-lipoic acid (0.5% w/w) for 2 wk, k illed and their liver parenchymal cells were isolated. Hepatocytes from unt reated old rats vs. young controls had significantly lower oxygen consumpti on (P<0.03) and mitochondrial membrane potential. (R)-Lipoic acid supplemen tation reversed the age-related decline in O-2 consumption and increased (P <0.03) mitochondrial membrane potential. Ambulatory activity, a measure of general metabolic activity, was almost threefold lower in untreated old rat s 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 fluores cence produced on oxidizing 2',7'-dichlorofluorescin, was significantly low ered in (R)-lipoic acid supplemented old rats (P<0.01). Malondialdehyde (MD A) levels, an indicator of lipid peroxidation, were increased fivefold with age in cells from unsupplemented rats. Feeding rats, the (R)-lipoic acid d iet reduced MDA levels markedly (P<0.01). Both glutathione and ascorbic aci d levels declined in hepatocytes with age, but their loss was completely re versed with (R)-lipoic acid supplementation. Thus, (R)-lipoic acid suppleme ntation improves indices of metabolic activity as well. as lowers oxidative stress and damage evident in aging.