Hopes Grow for Anti-Aging Drug:
Scientists Have Rejuvenated Aging Rats by Giving them a Cocktail of Dietary Supplements

Tory M. Hagen*, Jiankang Liu [dagger], [Dagger], Jens Lykkesfeldt, Carol M. Wehr [dagger], Russell T. Ingersoll [Dagger], Vladimir Vinarsky [dagger], James C. Bartholomew, and Bruce N. Ames [dagger] , [Dagger], [||], "Feeding Acetyl-L-Carnitine and Lipoic Acid to Old Rats Significantly Improves Metabolic Function While Decreasing Oxidative Stress," Proc. Natl. Acad. Sci. USA, Vol. 99, No. 4, pp. 1870-5 (February 19, 2002).

_______________________________________________

* Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331;
[dagger] Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720;
[Dagger] Children's Hospital Oakland Research Institute, Oakland, CA 94609;
 Department of Pharmacology and Pathobiology, Royal Veterinary and Agricultural University, Copenhagen DK-1870, DENMARK; and
 Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Contributed by Bruce N. Ames, December 28, 2001

[||] To whom reprint requests should be addressed: Children's Hospital Oakland Research Institute, 5700 Martin Luther King, Jr., Way, Oakland, CA 94609.
E-mail: bnames@ulink4.berkeley.edu.

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 O2 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.

Hopes Grow for Anti-Aging Drug:
Scientists Have Rejuvenated Aging Rats by Giving them a Cocktail of Dietary Supplements

The Breakthrough Raises Hopes that It Might One Day
Be Possible to Develop an Anti-Aging Drug for Humans:
"These Old Rats Got Up and Did the Macarena"

Tuesday, February 19, 2002, (BBC News) - The researchers gave a combination of two natural chemicals available in health food stores to the animals -- which were in the rat equivalent of their seventies. Lead researcher Prof Bruce Ames, of the University of California at Berkeley, said "the results were astonishing." He said: "With the two supplements together, these old rats got up and did the Macarena. The brain looks better, they are full of energy -- everything we looked at looks more like a young animal." The animals' memories were also significantly improved. The researchers estimate that the effect on the rats was the equivalent making a 75 to 80-year-old person act like he was middle-aged.

Found in the Body

The chemicals used in the experiment were Acetyl-L-Carnitine and Alpha-Lipoic Acid, both of which are normally found in the body's cells. Research like this provides the first step to developing treatments that will help to improve health in later life Acetyl-L-Carnitine (ALC) is sold as an energy-booster, while Alpha-Lipoic Acid (ALA) is sold as an antioxidant with anti-aging properties. The combination of the two chemicals has now been patented by the University of California at Berkeley. A company set up to exploit the patent, Juvenon , is already conducting human clinical trials. Three research papers on different animal studies of the chemicals have been published in the journal Proceedings of the National Academy of Sciences. The studies probed the biochemical action of the supplements, compared the behavior of old and young rats, and tested the memory of animals who were fed the compounds.

Cell Power House

The researchers found that the two chemicals in combination have a positive impact on mini-organs within the body's cells called mitochondria. Mitochondria generate energy within the cells, and research has suggested that their deterioration is an important cause of aging.

The problem seems to be that the very process of creating energy generates molecules called free radicals, which have a deeply destructive effect on the way cells work. The supplement combination was found to "mop up" the free radicals in mitochondria. It also boosts the activity of an enzyme fundamental to the energy-creating process. The research also showed that mitochondria in brain cells important to memory were less damaged by radicals in animals who were fed the supplements.

Important Research

Caroline Bradley, of the Charity Research into Aging, told BBC News Online that the study was clearly important. She said, "The big step forward is that they have found a way of getting anti-oxidant into the mitochondria themselves "Getting past the mitochondrial membrane has been the main challenge." She added that "it was early days for the research but that it was the first step towards improving human health in later life."