BioEd Online

Are you pumping iron but not bulking up? US scientists may soon know why. They are seeking the genes that predict whether training will transform you into a muscle-bound beefcake or leave you as you are.

If found, the genetic sequences could forecast athletic potential, risks of muscle wasting during old age or even which astronauts might lose bulk during space flight.

Over 900 subjects have already been recruited to the study, and 500 more are sought, says team member Eric Hoffman of the Children's National Medical Center in Washington. After enrollment, the team gauges the maximum weight that each person can lift using their non-writing arm, and uses magnetic resonance imaging to assess the size of the muscles in that arm.

The subjects then embark on an aggressive one-armed workout regime: pumping their biceps and triceps for 45 minutes twice a week for nearly three months. By the end, "some of them look really lopsided," says team leader Paul Thompson of Hartford Hospital in Connecticut.

When the training is complete, the researchers reassess the size of the muscles and select the 10% of subjects whose muscles bulked up the most, and the same fraction of those whose physique was least affected. They scan these people's DNA for genetic features they might have in common, focusing on single letter changes in around 100 genes already linked with strength and exercise.

The team has already tracked down 25 genetic signposts that characterize either the muscle-bound or the scrawny group, says Hoffman. He plans to publish the results later this year.

The study raises the prospect that genetic tests might one day be used to predict a person's risk of muscle problems as they age or after prolonged bed rest. Study of such genes may shed light on wasting diseases such as Duchenne muscular dystrophy. Hoffman hopes that the results might also reveal which of the genes could be targeted with drugs to aid these conditions.

More controversially, aspiring athletes might be tested to see if they have what it takes, genetically, to reach the top. This is a service that ambitious athletes might be keen to take up, experts say, but the psychological consequences are unknown. "Would it depress the heck out of you so you don't try?" asks Thompson.

Boy wonder

So far, scientists have tracked down only four genes that control the size of muscles and their response to training. Last month in the New England Journal of Medicine, for example, Markus Schuelke and his colleagues reported the case of an unusually strong five-year-old boy who carried a rare mutation in the myostatin gene². It is not yet clear whether more common differences in strength are caused by changes in the same gene.

Muscles are thought to contain a supply of stem cells that normally lie dormant, but which are prompted, after exercise or injury, into churning out new cells. Myostatin is thought to control the amount of fresh tissue generated by these stem cells.

The new study is the largest attempt to widen the search for strength-linked genes. "It's very ambitious," says Claude Bouchard who studies genetic variation and physical activity at Louisiana State University in Baton Rouge.