New hope for aging rats — and humans too?
Dietary supplements make elderly rats youthful, campus researchers report

Bruce Ames

27 February 2002 | 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 by campus scientists and Children’s Hospital Oakland Research Institute.

A team of researchers led by Bruce Ames, professor of molecular and cell biology, 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 Feb. 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, but 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.

“The brain looks better, they are full of energy — everything we looked at looks more like a young animal,” Ames said.

“The animals seem to have much more vigor and are much more active than animals not on this diet,” said former Berkeley post-doc fellow Tory Hagen, now at Oregon State University.

“And we also see a reversal in loss of memory,” he added. “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.”

One of the articles probes the reasons behind this rejuvenation, concluding that the two chemicals “tune up” the energy-producing organelles that power all cells, the mitochondria.

Ames said there is increasing evidence that deterioration of mitochondria is an important cause of aging. A significant cause of this deteriorating, he believes, is the accumulation of destructive free radicals 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 would achieve the latter. Experiments showed that this regimen worked.

Ames and Hagen have long had an interest in mitochondria as they relate to aging, and they were intrigued by a 1999 Italian study showing that acetyl-L-carnitine, when fed to old rats, improved mitochondrial activity.

The two thought this might be a way to reverse the effects of aging in mitochondria, and in various trials found it to work to some degree.

"We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat 7 to 10 months of age," Hagen said.

"This is equivalent to making a 75- to 80-year-old person act middle-aged,” he noted. “We've only shown short-term effects, but the results give us the rationale for looking at these things long term."

UC has patented use of the combination of the two supplements to rejuvenate cells. Ames and Hagen in 1999 founded a company called Juvenon to license the patent from the university. Juvenon currently is engaged in human clinical trials of the combination.