Two dietary supplements readily available in most health food stores have been shown to slow down the ageing process in rats, raising hopes that an anti-ageing pill for humans could soon be a reality.
Researchers at the University of California, Berkeley, and the Children's Hospital Oakland Research Institute, gave acetyl-L-carnitine and alpha-lipoic acid - both of which are widely sold as dietary supplements and which occur naturally in products such as red meat and milk - to older rats. The results showed that the rats had better memories, more energy and the mitochondria, energy-producing organelles in their cells, worked better.
Dr Bruce N. Ames, lead author of the study, writing in the 19 February issue of Proceedings of the National Academy of Sciences, 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 seem to have much more vigour and are much more active than animals not on this diet, signalling massive improvement to these animals' health and well-being," said Tory M. Hagen, a former UC Berkeley post-doctoral fellow and now assistant professor at the Linus Pauling Institute at Oregon State University, Corvallis.
"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 is currently engaged in human clinical trials of the combination.
The researchers also investigated the reasons behind the positive effects of the supplements, concluding that the two chemicals "tune up" the mitochondria. Both chemicals are normally used in mitochondria.
According to Ames, the mitochondria are the "weak link in ageing". There is substantial evidence to suggest that the deterioration of mitochondria is one of the principle reasons for ageing, and Ames believes that this deterioration in turn is due to the accumulation of destructive free radicals - by-products of normal metabolism - that disable enzymes and other chemicals.
The combination of the two chemicals can defeat the free radicals and boost the activity of a damaged enzyme, carnitine acetyltransferase, which plays a key role in burning fuel in mitochondria. The anti-oxidant alpha-lipoic acid does the former, while acetyl-L-carnitine, one of two proteins that the enzyme acts on, can achieve the latter, the researchers found.
They discovered that the enzyme carnitine acetyltransferase was less active in old rats than in young rats, and that it bound 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."
Another part of the study involved looking at the energising effects of the combination therapy. Rats aged two to four months were compared with those aged 24 to 28 months, all of them fed acetyl-L-carnitine in their water and alpha-lipoic acid in their food.
After as much as a month on the supplements, the old and lethargic rats became more energetic. "We significantly reversed the decline in overall activity typical of aged rats to what you see in a middle-aged to young adult rat seven to 10 months of age," Hagen said. "This is equivalent to making a 75- to 80-year-old person act middle-aged. We've only shown short-term effects, but the results give us the rationale for looking at these things long term."
They also found that the combination of lipoic acid and acetyl-carnitine improved mitochondrial activity and thus cellular metabolism, and increased levels of various chemicals known to decline with age, including ascorbic acid, an antioxidant.
In a third study, the researchers fed old rats a similar diet of the two supplements and looked at memory function as measured by the Morris water maze test and a peak procedure for assessing temporal or time-based memory developed by Seth Roberts, professor of psychology at UC Berkeley.
They found that supplementation improved both spatial and temporal memory, and reduced the amount of oxidative damage to RNA in the brain's hippocampus, an area important in memory. In electron microscope pictures of cells from the hippocampus, mitochondria showed less structural decay in old rats that had a supplemented diet.