Researchers at the Salk Institute for Biological Studies, and two Swiss institutions, (Ecole Polytechnique Federale de Lausanne (EPFL) and the University of Lausanne) recently determined that altering a gene can make muscles (in mice and nematodes) twice as strong. Their discovery opens up the possibilities of treating age related muscle degeneration or genetically caused muscle degeneration.
The team of scientists found that a tiny inhibitor in the body may be responsible for determining the strength of our muscles. By acting on a receptor (NCoR1) in order to modulate the transcription (the copying of DNA into a similar RNA form) of certain genes, the scientists managed to create strong, high-endurance mice and worms by suppressing a natural muscle-growth inhibitor. Essentially the scientists started to “knock out” the function of this corepressor to create mice that were twice as strong as normal mice and ran 60% faster when monitored. Johan Auwerx, the lead author from EPFL, says that molecules such as NCoR1 decrease the activity of genes. By mutating or chemically changing this property of NCoR1, “gene circuits” can be made to provide more energy to muscles.
Furthermore, the researchers were able to suppress NCoR1 in the offspring of the mice by genetically manipulating them. With this inhibitor absent, it was noted that muscle tissue developed more effectively. Apparently mice that were modified even showed better resistance to cold. Examination under a microscope confirmed that the muscle fibres of the modified mice were denser and bigger. Additionally the cells in the tissue contained a higher number of mitochondria; hence providing the muscle with more energy.
“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.”
The study was also conducted on nematode worms and showed similar results (especially increased mitochondria). The scientists hence concluded that their results could be applied to a large range of creatures, possibly even humans. “This could be used to combat muscle weakness in the elderly, which can lead to falls and contributes to hospitalizations,” Auwerx says. “In addition, we think that this could be used as a basis for developing a treatment for genetic muscular dystrophy.”
The group of scientists have not yet detected any side effects associated with eliminating the NCoR1 receptor. Although the experiments involved genetic manipulations, the researchers are already investigating potential drug molecules that could be used to reduce the receptor’s effectiveness as they clearly view this finding with keen interest.