InterventionR-Alpha-Lipoic Acid
Alternate Name
OrganismRattus norvegicus
Aging PhenotypeN/A
Allele TypeN/A
StrainFischer 344
DescriptionDietary supplementation with acetyl-L-carnitine (ALCAR) and/or R-alpha-lipoic acid (LA), two mitochondrial metabolites, partially reversed the age-related decline in hepatocyte mitochondrial membrane potential and increased oxygen consumption by these cells (Hagen, 2002). ALCAR+LA also reduced age-associated mitochondrial structural decay in the hippocampus (Liu, 2002(1)). ALCAR+LA appeared to ameliorate oxidative stress, increasing celluar levels of ascorbate (which declines with age due to oxidative stress) to the level observed in young rats, and reducing levels of malondialdehyde (which increases with age due to oxidative stress) to the level of young rats (Hagen, 2002). Furthermore, ALCAR+LA reduced the extent of age-associated nucleic acid oxidation in the hippocampus (Liu, 2002(1)). This feeding regimen increased ambulatory activity in young and old rats, with the increase being significantly greater in old than in young rats (Hagen, 2002). ALCAR+LA also partially reversed the decline in performance in tests of spatial and temporal memory in old rats relative to young rats (Liu, 2002(1)).
Gene FunctionN/A
Other PhenotypesFunction of the mitochondrial enzyme carnitine acetyltransferase (CAT) declines with age due to a decrease in activity and in substrate binding affinity; this decline can be reversed by feeding old rats with ALCAR+LA (Liu, 2002(2)).
Primary ReferenceHagen, T. M., Liu, J., Lykkesfeldt, J., Wehr, C. M., Ingersoll, R. T., Vinarsky, V., Bartholomew, J. C., and Ames, B. N. (2002). Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative st [Abstract]
Other ReferencesHagen, T. M., Ingersoll, R. T., Wehr, C. M., Lykkesfeldt, J., Vinarsky, V., Bartholomew, J. C., Song, M. H., and Ames, B. N. (1998). Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci U [Abstract]
Liu, J., Head, E., Gharib, A. M., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., and Ames, B. N. (2002). Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine a [Abstract]
Liu, J., Killilea, D. W., and Ames, B. N. (2002). Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid [Abstract]
Relevant Links
KeywordsRattus norvegicus, rat, metabolism, feeding, dietary supplementation, antioxidants, mitochondria, oxidative stress, diet, metabolites