Researchers Identify Gene That Enhances Muscle Performance

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Researchers Identify Gene That Enhances Muscle Performance

http://www.sciencedaily.com/releases/2006/11/061116084058.htm

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 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. "

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.

" 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. "

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 many enzyme genes are thought to only be active in just one

tissue. "

Other authors on the paper include Barré,

, and Fiering, all at Dartmouth; Hirshman

and Laurie Goodyear of Joslin Diabetes Center in Boston; ph

Brozinick with Eli Lilly and Company; and Bruce Kemp of the St.

's Institute in Australia.

This research is funded by the National Institutes of Health.

Note: This story has been adapted from a news release issued by

Dartmouth College.