Acetyl-L-Carnitine Fed to Old Rats Partially Restores Mitochondrial Function and Ambulatory Activity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 16; pp. 9562 - 9566
• Main Authors: Hagen, Tory M., Ingersoll, Russell T., Wehr, Carol M., Lykkesfeldt, Jens, Vinarsky, Vladimir, Bartholomew, James C., Song, Mi-Hye, Ames, Bruce N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 04-08-1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Acetylcarnitine - administration & dosage; Acetylcarnitine - pharmacology; Administration, Oral; Aging; Aging - metabolism; Animals; Biological Sciences; Cardiolipins; DNA damage; Electrons; Fluorescence; Hepatocytes; Liver; Male; Metabolism; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Mitochondrial membranes; Motor Activity - drug effects; Oxidation; Oxygen Consumption; Rats; Rats, Inbred F344; Rodents; Young animals
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.16.9562

Mitochondrial function and ambulatory activity were monitored after feeding old rats acetyl-L-carnitine (ALCAR). Young (3-5 mo) and old (22-28 mo) rats were given a 1.5% (wt/vol) solution of ALCAR in their drinking water for 1 mo, were sacrificed, and their liver parenchymal cells were isolated. ALCAR supplementation significantly reverses the age-associated decline of mitochondrial membrane potential, as assessed by rhodamine 123 staining. Cardiolipin, which declines significantly with age, is also restored. ALCAR increases cellular oxygen consumption, which declines with age, to the level of young rats. However, the oxidant production per oxygen consumed, as measured by 2′,7′-dichlorofluorescin fluorescence levels, is ≈ 30% higher than in untreated old rats. Cellular glutathione and ascorbate levels were nearly 30% and 50% lower, respectively, in cells from ALCAR-supplemented old rats than in untreated old rats, further indicating that ALCAR supplementation might increase oxidative stress. Ambulatory activity in young and old rats was quantified as a general measure of metabolic activity. Ambulatory activity, defined as mean total distance traveled, in old rats is almost 3-fold lower than in young animals. ALCAR supplementation increases ambulatory activity significantly in both young and old rats, with the increase being larger in old rats. Thus, ALCAR supplementation to old rats markedly reverses the age-associated decline in many indices of mitochondrial function and general metabolic activity, but may increase oxidative stress.