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A Gene That Enhances Muscle Performance

A Gene That Enhances Muscle Performance Dartmouth researchers (l-r) Lee Witters, Christine Richardson, and Laura Barré. (Photo by Joseph Mehling '69
A team of researchers, led by researchers at Dartmouth Medical School and Dartmouth College, have identified and tested a gene that dramatically alters both muscle metabolism and performance. The scientists say that this finding could someday lead to therapy for muscle diseases, including helping the elderly who suffer from muscle deterioration and improving muscle performance in endurance athletes.

The scientists 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 especially striking feature of the finding was the accumulation of muscle glycogen, the stored form of carbohydrates, a condition that a number of 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 previous exercise regimen, the mouse developed a number of of the muscle features that would only be observed after a period of exercise training".

Witters, whose lab led the study, explains that this finding has implication for anyone with a muscle disease and particularly 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. As per Witters, there is tremendous interest in the geriatric field to find ways to improve muscle performance.

"We now wonder if it's possible to achieve elements of muscular fitness without having to exercise, which in turn, raises a number of 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".

Witters says that the carbohydrate, glucose, is a major fuel that powers muscles, and this contributes directly to a muscle's ability to repetitively contract during exercise. The activated AMPK in the Dartmouth mouse appears to have increased glycogen content by actually switching on a gene that normally synthesizes liver glycogen.

"The switching on of this liver gene in muscles," he says, "is a shift in the conception of the biochemistry of muscle metabolism, since a number of enzyme genes are thought to only be active in just one tissue".


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

Medicineworld.org: A Gene That Enhances Muscle Performance

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