Ironman 2.0

Biologists enhance endurance with genetically altered muscles.

By Jennifer Barone|Wednesday, May 30, 2007

With a genetic tweaking of muscle fibers, Harvard University cell biologist Bruce Spiegelman turned ordinary mice into rodent triathletes. The study raises the question of whether something similar could work—or be at work—in humans.

Muscle fibers are characterized as either slow or fast, Spiegelman explains. “The slow ones are generally oxidative endurance muscles” like the muscles in your back that help in maintaining posture. They don’t contract very rapidly, but they process oxygen efficiently and can be used comfortably for long periods. Fast muscle fibers have speedy reaction times, but they run out of steam quickly, making them better for short bursts of activity.

Spiegelman studies a kind of muscle fiber known as type IIX, which falls between the typical fast and slow categories. “Less is known about IIX than any other muscle type,” he says, though it seems to provide a combination of speed and endurance. He recently found a master gene, called PGC-1beta, that when switched on can convert almost all the muscle fibers in mice to IIX. When the IIX mice were put on treadmills, they ran for 25 percent longer and covered 45 percent more distance than their normal littermates.

In humans, Spiegelman says, muscle type is due to a combination of genetics and experience. Some kinds of muscle fiber seem fairly stable and are probably inherited, but others can be converted through exercise. For example, distance training causes fibers to change into endurance types. Spiegelman is screening drugs that could exploit this genetic switch to trigger muscle fiber conversions like the one in his IIX mice. Drugs that turn on PGC-1beta could be used to treat muscle-wasting diseases like muscular dystrophy—or to create superathletes. “Are we worried that this could be misused?” he asks. “Yes, we’re concerned, but we’re hunting bigger game than that. We’re doing what we need to do to help people.”

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