Tweaking A Gene Makes Muscles Twice As Strong

An international team of scientists has created super-strong, high-endurance mice and worms by suppressing a natural muscle-growth inhibitor, suggesting treatments for age-related or genetics-related muscle degeneration are within reach. The project was a collaboration between researchers at the Salk Institute for Biological Studies, and two Swiss institutions, Ecole Polytechnique Federale de Lausanne (EPFL) and the University of Lausanne.

The scientists found that a tiny inhibitor may be responsible for determining the strength of our muscles. By acting on a genome regulator (NCoR1), they were able to modulate the activity of certain genes, creating a strain of mighty mice whose muscles were twice a strong as those of normal mice.

"There are now ways to develop drugs for people who are unable to exercise due to obesity or other health complications, such as diabetes, immobility and frailty," says Ronald M. Evans, a professor in Salk's Gene Expression Lab, who led the Salk team. "We can now engineer specific gene networks in muscle to give the benefits of exercise to sedentary mice."

Johan Auwerx, the lead author from EPFL, says molecules such as NCoR1 are molecular brakes that decrease the activity of genes. Releasing the brake by mutation or with chemicals can reactivate gene circuits to provide more energy to muscle and enhance its activity.

In an article appearing in the journal Cell, the Salk researchers and their collaborators reported on the results of experiments done in parallel on mice and nematodes. By genetically manipulating the offspring of these species, the researchers were able to suppress NCoR1, which normally acts to inhibit the buildup of muscle tissues.

In the absence of the inhibitor, the muscle tissue developed much more effectively. The mice with the mutation became true marathoners, capable of running faster and longer before showing any signs of fatigue. In fact, they were able to cover almost twice the distance run by mice that hadn't received the treatment. They also exhibited better cold tolerance.