November 25, 2011
Tweaking a Gene Makes Muscle Twice as Strong
(Ivanhoe Newswire) — Super strong mice and marathon mice and nematodes were created by reducing the function of a natural inhibitor, suggesting treatments for age-related or genetically caused muscle degeneration are within reach.
It turns out that a tiny inhibitor may be responsible for how strong and powerful our muscles can be. This is the surprising conclusion reached by scientists in EPFL's Laboratory of Integrative Systems Physiology (LISP), in collaboration with a group in the Center for Integrative Genomics at the University of Lausanne and at the Salk Institute in California. By acting on a receptor (NCoR1), they were able to modulate the transcription of certain genes, creating a strain of mighty mice whose muscles were twice as strong as those of normal mice.Transcription consists of creating proteins in an organism in response to instructions contained in its DNA, and this process if modulated by cofactors. Cofactors either aid in transcription or suppress it.
In this study, led by EPFL profession Johan Auwerx, experiments were done in parallel on mice and nematodes. By genetically manipulating the offspring of these species, the researchers were able to suppress the NCoR1 corepressor, which normally acts as a cofactors that inhibits buildup of muscle tissue.
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.
Unlike previous experiments with so-called super mice, this study addresses the way energy is burned in the muscle and the way the muscle is built. Examination under a microscope confirmed that the muscle fibers of the modified mice are denser, the muscles are more massive, and the cells in the tissue contain higher numbers of mitochondria--cellular organelles that deliver energy to the muscles.
Similar results were also observed in nematode worms, allowing the scientists to conclude that their results could be applicable to a large range of living creatures.
According to a second article published in the same journal and also involving EPFL's LISP Laboratory, suppressing the NCoR1 receptor in adipose tissues (fat) also led to interesting results. By acting on this corepressor, it was possible to fundamentally change the corpulence of the mice being studied without inducing weight-related diseases. "The specimens that became obese via this treatment did not suffer from diabetes, unlike mice who become obese for other reasons," notes Auwerx.
The scientists have not yet detected any deleterious side effects associated with eliminating the NCoR1 receptor from muscle and fat tissues, and although the experiments involved genetic manipulations, the researchers are already investigating potential drug molecules that could be used to reduce the receptor's effectiveness.
"This could be used to combat muscle weakness in the elderly, which leads to falls and contributes to hospitalizations," explained Auwerx. "In addition, we think that this could be used as a basis for developing a treatment for genetic muscular dystrophy."
If these results are confirmed in humans, there's no question it will attract interest from athletes as well as medical experts. "It will be important for anti-doping authorities to monitor that these treatments are not used in an unauthorized manner," concluded Auwerx.
SOURCE: Cell, published online November 10, 2011