Dartmouth researchers have found yet another way to make mice have big muscles without exercise.

A team of researchers, led by scientists at Dartmouth Medical School and Dartmouth College, have identified and tested a gene that dramatically alters both muscle metabolism and performance. The researchers say that this finding could someday lead to treatment for muscle diseases, including helping the elderly who suffer from muscle deterioration and improving muscle performance in endurance athletes.

The ban on so-called "gene doping" or gene therapy by many athletic associations slows the rate of progress for the development of gene therapies that increase musculature. Eventually the athletic associations are going to split over this issue. New athletic associations will form that allow genetic engineering. Those associations and companies will put on competitions between the genetically enhanced that eclipse the competitions between natural humans.

Want big muscles without all the hard work? Genetic engineering of an enzyme is the ticket.

The researchers report that the enzyme called AMP-activated protein kinase (or AMPK) is directly involved in optimizing muscle activity. The team bred a mouse that genetically expressed AMPK in an activated state. Like a trained athlete, this mouse enjoyed increased capacity to exercise, manifested by its ability to run three times longer than a normal mouse before exhaustion. One particularly striking feature of the finding was the accumulation of muscle glycogen, the stored form of carbohydrates, a condition that many athletes seek by "carbo-loading" before an event or game. The study appears in the Nov. 14 online issue of the American Journal of Physiology: Endocrinology and Metabolism.

"Our genetically altered mouse appears to have already been an exercise program," says Lee Witters, the Eugene W. Leonard 1921 Professor of Medicine and Biochemistry at Dartmouth Medical School and professor of biological sciences at Dartmouth College. "In other words, without a prior exercise regimen, the mouse developed many of the muscle features that would only be observed after a period of exercise training."

Even if you were genetically engineered to grow big muscles naturally there might still be health benefits to exercise such as development of better arteries and veins. But then that just calls out for gene therapy the circulatory system to compensate for the lack of exercise there too.

The ability to stimulate muscle growth would bring great benefits to elderly people with shrivelled muscles. Okay scientists, figure this out before we get much older.

Witters, whose lab led the study, explains that this finding has implication for anyone with a muscle disease and especially for the growing proportion of the population that is aging. Deteriorating muscles often make the elderly much more prone to fall, leading to hip and other fractures. According to Witters, there is tremendous interest in the geriatric field to find ways to improve muscle performance.

Of course athletes will use gene therapy to enhance muscle strength as soon as it becomes possible.

"We now wonder if it's possible to achieve elements of muscular fitness without having to exercise, which in turn, raises many questions about possible modes of exercise performance enhancement, including the development of drugs that could do the same thing as we have done genetically," he says. "This also might raise to some the specter of 'gene doping,' something seriously being talked about in the future of high-performance athletes."

Gene doping will take off long before it becomes safe to use. Old folks will benefit from the willingness of athletes to take risks with new biotechnologies. The athletes will serve as very willing guinea pigs.