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Dietary Supplements Make Old Rats Youthful, May Help Rejuvenate Aging Humans, According To UC Berkeley Study

Two dietary supplements straight off the health food store shelf put the spark back into aging rats, and might do the same for aging baby boomers, according to a study at the University of California, Berkeley, and Children’s Hospital Oakland Research Institute.

A team of researchers led by Bruce N. Ames, professor of molecular and cell biology at UC Berkeley, fed older rats two chemicals normally found in the body’s cells and available as dietary supplements: acetyl-L-carnitine and an antioxidant, alpha-lipoic acid. 

In three articles in the February 19 issue of Proceedings of the National Academy of Sciences, Ames and his colleagues report the surprising results. Not only did the older rats do better on memory tests, they had more pep, and the energy-producing organelles in their cells worked better. 

“With the two supplements together, these old rats got up and did the Macarena,” said Ames, also a researcher at Children’s Hospital Oakland Research Institute (CHORI). “The brain looks better, they are full of energy - everything we looked at looks more like a young animal.” 

“The animals seem to have much more vigor and are much more active than animals not on this diet, signaling massive improvement to these animals’ health and well-being,” said former UC Berkeley post-doctoral fellow Tory M. Hagen, now an assistant professor at the Linus Pauling Institute at Oregon State University, Corvallis. “And we also see a reversal in loss of memory. That is a dual-track improvement that is significant and unique. This is really starting to explode and move out of the realm of basic research into people.” 

Based on the group’s earlier studies, the University of California patented use of the combination of the two supplements to rejuvenate cells. Ames, through the Bruce and Giovanna Ames Foundation, and Hagen founded a company in 1999 called Juvenon to license the patent from the university. Juvenon currently is engaged in human clinical trials of the combination. 

One of the three PNAS articles probes the reasons behind this rejuvenation, concluding that the two chemicals “tune up” the energy-producing organelles that power all cells, the mitochondria. Both chemicals are normally used in mitochondria. 

Ames calls mitochondria the “weak link in aging.” Evidence has been piling up, he said, that deterioration of mitochondria is an important cause of aging. A significant cause of this deterioration, he believes, is the accumulation of destructive free radicals - byproducts of normal metabolism - that disable enzymes and other chemicals. 

The combination therapy targets mitochondria to get rid of destructive radicals and to boost the activity of a damaged enzyme, carnitine acetyltransferase, that plays a key role in burning fuel in mitochondria. The researchers hoped that the anti-oxidant alpha-lipoic acid would do the former, and that flooding the cell with acetyl-L-carnitine, one of two proteins that the enzyme acts on, would achieve the latter. 

Experiments showed that this regimen worked. Associate researcher Jiankang Liu of CHORI, UC Berkeley postdoctoral fellow David W. Killilea and Ames demonstrated that the enzyme carnitine acetyltransferase is less active in old rats than in young rats, and that it binds less tightly to acetyl-L-carnitine in older rats. 

Supplementation with acetyl-L-carnitine or a combination of acetyl-L-carnitine and alpha-lipoic acid restored the enzyme’s activity nearly to that found in young rats and substantially restored binding to acetyl-L-carnitine. 

“The acetyl-L-carnitine is protecting the protein and the higher levels are enabling the protein to work, while alpha-lipoic acid knocks down oxygen radicals,” Ames said. “Each chemical solves a different problem - the two together are better than either one alone.” 

Ames and Hagen have long had an interest in mitocho

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