TitleFeeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress.
Publication TypeJournal Article
Year of Publication2002
AuthorsHagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN
JournalProc Natl Acad Sci U S A
Date Published2002 Feb 19
KeywordsAcetylcarnitine, Age Factors, Animals, Antioxidants, Ascorbic Acid, Fluoresceins, Hepatocytes, Lipid Peroxidation, Male, Malondialdehyde, Nootropic Agents, Oxidative Stress, Oxygen, Protein Binding, Rats, Rats, Inbred F344, Thioctic Acid, Time Factors

Mitochondrial-supported bioenergetics decline and oxidative stress increases during aging. To address whether the dietary addition of acetyl-l-carnitine [ALCAR, 1.5% (wt/vol) in the drinking water] and/or (R)-alpha-lipoic acid [LA, 0.5% (wt/wt) in the chow] improved these endpoints, young (2-4 mo) and old (24-28 mo) F344 rats were supplemented for up to 1 mo before death and hepatocyte isolation. ALCAR+LA partially reversed the age-related decline in average mitochondrial membrane potential and significantly increased (P = 0.02) hepatocellular O(2) consumption, indicating that mitochondrial-supported cellular metabolism was markedly improved by this feeding regimen. ALCAR+LA also increased ambulatory activity in both young and old rats; moreover, the improvement was significantly greater (P = 0.03) in old versus young animals and also greater when compared with old rats fed ALCAR or LA alone. To determine whether ALCAR+LA also affected indices of oxidative stress, ascorbic acid and markers of lipid peroxidation (malondialdehyde) were monitored. The hepatocellular ascorbate level markedly declined with age (P = 0.003) but was restored to the level seen in young rats when ALCAR+LA was given. The level of malondialdehyde, which was significantly higher (P = 0.0001) in old versus young rats, also declined after ALCAR+LA supplementation and was not significantly different from that of young unsupplemented rats. Feeding ALCAR in combination with LA increased metabolism and lowered oxidative stress more than either compound alone.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID11854487
PubMed Central IDPMC122286
Grant ListR01 AG017141 / AG / NIA NIH HHS / United States
AG17140 / AG / NIA NIH HHS / United States
AG17141 / AG / NIA NIH HHS / United States
P30 ES001896 / ES / NIEHS NIH HHS / United States
P30-ES01896 / ES / NIEHS NIH HHS / United States