(photo credit: Bloomberg)
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 Laboratory, 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 last week 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
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.
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previous experiments that focused on "genetic accelerators" this work shows that
suppressing an inhibitor is a new way to build muscle. 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
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.
The scientists have not yet detected any
harmful side effects associated with eliminating the NCoR1 receptor from muscle
and fat tissues. Although the experiments involved genetic manipulations, the
researchers are already investigating potential drug molecules that could be
used to reduce the receptor's effectiveness.
The researchers say their
results are a milestone in our understanding of certain fundamental mechanisms
of living organisms, in particular the little-studied role of corepressors
---molecules that inhibit the expression of genes. In addition, they give a
glimpse at possible long-term therapeutic applications.
"This could be
used to combat muscle weakness in the elderly, which leads 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
He added that if these results are confirmed in humans, there's no
question they will attract interest from athletes as well as medical experts.This article was fist published at: www.newswise.com
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