Working out is tough. So why not skip the exercise and pop a few endurance-boosting pills?

That dream, cherished by millions of sedentary couch potatoes, just got a little bit closer. Today, researchers are reporting that an experimental drug can mimic the results of an exercise regimen – with no exercise required. After four weeks of taking the pill, mice who hadn't worked out displayed a 44 percent increase in their running endurance.

"It’s tricking the muscle into ‘believing’ it’s been exercised daily," said the study's lead researcher, Ronald Evans of the Salk Institute, in a release. "It’s basically the couch potato experiment, and it proves you can have a pharmacologic equivalent to exercise."

Human muscle enhancement has already shown considerable success. Steroids easily facilitate the creation of bulky muscles. But that type of muscle-building doesn't necessarily help you run a 10k, and endurance-based exercise tends to yield more health benefits than strength training. If drugs like this work in humans, it could prove a boon to an aging and increasingly overweight American population.

But not all researchers are convinced that "exercise in a pill" is actually possible.

"Physical activity is so important for maintaining the health of the human body in almost every human organ system," said Darrell Neufer, a professor of sports medicine specializing in cellular energy systems at

East Carolina University. "It's going to be nearly impossible to create a pill that will mimic all the benefits that exercise has."

Neufer cited a 2000 paper by BYU and Washington University scientists that, he said, showed the drug the Salk Institute scientists used "does not fully mimic the adaptive response to exercise."

Until this study, only high doses of resveratol, a possible anti-aging drug and metabolic enhancer, had shown promise increasing endurance by enhancing mitochondrial function. But resveratol works by stimulating an entirely different set of proteins and could have a wider range of effects, for good or ill.

The new work, which appears today in the journal Cell, tries to tackle the cellular energy problem that we call fatigue directly, by activating the enzyme AMPK with a long-known drug called AICAR.

Scientists believe that AMPK is an important regulator of the cell's metabolism. In that energy system, ATP is used to power cellular action, such as the muscle contractions associated with running. In the process, ATP

breaks down into another substance called AMP. As that happens,

British researchers have shown that AMPK acts to crank up ATP production.

The drug, AICAR, mimics AMP, effectively tricking the body into thinking that it needs more energy and to begin producing more ATP – making more energy available for cellular action.

In other words, if ATP is the "molecular currency" of cellular energy transfer, AMPK is the mint that can print more money, and the drug is a kind of forged note from the Treasury Secretary ordering the mint to begin printing more bills.

Neufer, however, questioned the novelty of the research around AICAR, saying that the compound has long been linked to the creation of mitochondria – cells' engines – which, in turn, create more ATP.

"The bottom line is that the main finding is not a particularly new finding," Neufer said. "I'm surprised that this got into such a high-profile journal."

Still, the molecules Evans is studying have athletic authorities worried because they appear to increase endurance among trained athletes. In the same Cell paper, the researchers showed that, using a separate drug, they could increase the levels of a protein called PPAR-delta, which resulted in a

68 percent endurance gain for exercise-trained mice.

Evans is already working with the World Anti-Doping Agency to find a way to test for this new kind of doping. It won't be ready by this year's summer Olympics, but the test could be ready in time to retroactively test the blood samples from athletes who compete in the 2008 games.

Neufer agreed that human athletes need to be cautious about trying to obtain pharmacological help.

"Right now you have no way to target the drug to specific cell types. By giving Aicar systemically, you'd be activating the signaling pathway in every cell of the body," he said. "Without knowing what impacts that might have that would be a dangerous thing to do."

Cell: AMPK and PPAR? Agonists Are Exercise Mimetics (abstract)

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