Scientists at Dana-Farber Cancer Institute have isolated a previously unknown protein in muscles that spurs their growth and increased power following resistance exercise. They suggest that artificially raising the protein's levels might someday help prevent muscle loss caused by cancer, prolonged inactivity in hospital patients, and aging.
Mice given extra doses of the protein gained muscle mass and strength, and rodents with cancer were much less affected by cachexia, the loss of muscle that often occurs in cancer patients, according to the report in the Dec. 7 issue of the journal Cell.
"This is basic science at present," commented Jorge Ruas, PhD, first author of the report. "But if you could find a way to elevate levels of this protein, that would be very exciting. For example, you might be able to reduce muscle wasting in patients in intensive care units whose muscles atrophy because of prolonged bed rest." Other applications, he said, might be in disorders such as muscular dystrophy and the gradual loss of muscle mass from aging.
Bruce Spiegelman, PhD, the senior author, led the Dana-Farber team that identified the protein, PGC-1 alpha-4, in skeletal muscle and said it is present in mice and humans. Resistance exercise, such as weight lifting, causes a rise in PGC-1 alpha-4, which in turn triggers biochemical changes that make muscles larger and more powerful, said the researchers.
The protein is an isoform, or slight variant, of PGC-1 alpha, an important regulatory of body metabolism that is turned on by forms of exercise, such as running, that increase muscular endurance rather than size. "It's pretty amazing that two proteins made by a single gene regulate the effects of both types of exercise," commented Spiegelman.
The researchers found that the new protein controls the activity of two previously known molecular pathways involved in muscle growth. A rise in PGC-1 alpha-4 with exercise increases activity of a protein called IGF1 (insulin-like growth factor 1), which facilitates muscle growth. At the same time, PGC-1alpha4 also represses another protein, myostatin, which normally restricts muscle growth. In effect, PGC-1 alpha-4 presses the accelerator and removes the brake to enable exercised muscles to gain mass and strength.
"All of our muscles have both positive and negative influences on growth," Spiegelman explained. "This protein (PGC-1 alpha-4) turns down myostatin and turns up IGF1."
Several experiments demonstrated the muscle-enhancing effects of the novel protein. The investigators used virus carriers to insert PGC-1 alpha-4 into the leg muscle of mice and found that within several days their muscle fibers were 60 percent bigger compared to untreated mice. They also engineered mice to have more PGC-1 alpha-4 in their muscles than normal mice who were not exercising. Tests showed that the treated mice were 20 percent stronger and more resistant to fatigue than the controls; in addition, they were leaner than their normal counterparts.
Mice engineered to have extra PGC-1 alpha-4 showed "dramatic resistance" to cancer-related muscle wasting, the scientists found. The mice lost only 10 percent mass in a leg muscle compared to a 29 percent loss in mice with cancer that did not have additional PGC-1 alpha-4, according to the report. The altered mice were also stronger and more active than the normal mice.
Dana-Farber Cancer Institute: http://www.dfci.harvard.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Pigs ‘edited’ with a warthog gene to resist African swine fever could help spawn GM animal farms in the UK
Mouse House to make naturalist biopic, six years after box-office failure of Creation, starring Paul Bettany
International team spends 10 years making inroads into treatment of bacterium which kills up to half of those it infects
You may not know it, but you probably have some Neanderthal in you. For people around the world, except sub-Saharan Africans, about 1 to 3 percent of their DNA comes from Neanderthals, our close cousins who disappeared roughly 39,000 years ago.
Research at Yale plotted what happened in the brains of two scientists as they held a conversation
From medicines to jet fuel, we have so many reasons to celebrate the microbes we live with every day
Genome sequencing indicates Kennewick Man is Native American, reopening the bitter battle over whether he should be reburied or studied
In the article on the discovery of dinosaurs (They’re back, Review, 6 June) you state: “In Sussex, a local doctor uncovered fragmentary remains of what appeared to be two more species of colossal extinct land reptiles.” You grossly underplay the contribution of Lewes-born Gideon Mantell, geologist and palaeontologist, author and diarist, friend to princes and international scholars as well as local doctor. Mantell not only discovered (aided by his wife) the first remains of the iguanodon in 1824 but named it – as it resembled the tooth of an iguana. This was the first known land dinosaur, Mary Anning having identified the first sea-living dinosaur.Mantell went on to put together more pieces of the jigsaw with extra fossil discoveries. In contrast to Richard Owen, whose models form the basis for the Crystal Palace dinosaurs, Mantell stated correctly that iguanodon would have walked on their back legs, using their forearms to fight or gather food. He did, however, attribute the thumb spike to a nose horn though later corrected this assumption. The Natural History Museum has a display on Gideon and his wife Mary’s contribution as well as the large “Mantell-piece” of Iguanodon fossils that he had on show in his museum in Brighton. He sold it, along with many more priceless items, to the British Museum in 1838. Gideon Mantell’s reputation deserves better than your throwaway remark. Debby MatthewsLewes, East Sussex Continue reading...
Unique triangular hairs help keep Saharan silver ants cool at 70°C by manipulating the physics of light
Most animals wouldn't confront a fearsome predator like a lion. But through sophisticated group work, hyenas launch successful raids