title: Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
authors.forename: Tory M
authors.initials: TM
authors.lastname: Hagen
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Jens
authors.initials: J
authors.lastname: Lykkesfeldt
authors.forename: Carol M
authors.initials: CM
authors.lastname: Wehr
authors.forename: Russell T
authors.initials: RT
authors.lastname: Ingersoll
authors.forename: Vladimir
authors.initials: V
authors.lastname: Vinarsky
authors.forename: James C
authors.initials: JC
authors.lastname: Bartholomew
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000108:Acetylcarnitine / Q000737:chemistry* / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism; D005452:Fluoresceins / Q000494:pharmacology; D022781:Hepatocytes / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018697:Nootropic Agents / Q000494:pharmacology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D008063:Thioctic Acid / Q000737:chemistry* / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000975:Antioxidants; D005452:Fluoresceins; D018697:Nootropic Agents; C029569:diacetyldichlorofluorescein; D008315:Malondialdehyde; D000108:Acetylcarnitine; D008063:Thioctic Acid; D001205:Ascorbic Acid; D010100:Oxygen