To restore aged muscles, block myostatin
The key to making up for age-related loss of muscle mass has been found
LifeSciencesToday based on Johns Hopkins Medicine:
Hopkins Researchers Solve Key Part Of Old Mystery In Generating Muscle MassThe results of a new study conducted by Johns Hopkins University scientists convincingly confirm the theory that age-related loss of muscle mass can be compensated in the absence of a fully functional resource of muscle stem cells.
"This is good news for patients with muscular dystrophy and other types of muscle atrophy associated with the weakening of stem cell function," says Se-Jin Lee, MD, professor of molecular biology and genetics at Johns Hopkins University School of Medicine, commenting on the results of experiments on mice., PhD., lead author of an article published in the journal Proceedings of the National Academy of Sciences (Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway, in the public domain).
In adult mammals, including humans, muscle stem cells, known as satellite cells, tend to be dormant. Exercise or injury stimulates their division and fusion either with each other or with nearby muscle fibers, which allows you to increase or replace the lost muscle mass. In atrophic muscular disorders, such as muscular dystrophy, muscle degeneration first activates the regeneration of lost tissues by satellite cells, but eventually this regenerative resource is exhausted and the balance shifts towards degeneration.
The mechanism of preserving and increasing muscle mass under normal conditions, in the absence of injuries, including the role of myostatin, a protein secreted by muscle cells that stops muscle growth, remains poorly understood. Blocking the function of myostatin in normal mice leads to an increase in muscle mass by 25-50 percent. But exactly which cells receive the myostatin signal and react to it remains unknown. Today, both satellite and muscle cells themselves are suspected of this.
To find out whether satellite cells are necessary for the realization of the function of myostatin, American scientists used three approaches. First, they examined specially bred mice with severe defects in either the function or the number of satellite cells. When blocking myostatin function (with the help of chemicals or genetic engineering) in both types of mice, muscle mass continued to increase significantly compared to that in mice with normal satellite cell function. These results meant that myostatin could act at least partially independently of satellite cells.
Mice without the myostatin gene (right) have almost twice as much muscle mass as normal animals.
Photo: Se-Jin Lee Lab.
Secondly, scientists have suggested that if myostatin directly suppresses the growth of satellite cells, their number should increase in the absence of myostatin. The researchers labeled the satellite cells with a persistent dye, and then suppressed myostatin function with a chemical. As expected, the muscle mass of the mice increased significantly, but the number of satellite cells remained the same. Their more active fusion with muscle fibers was also not observed. According to Professor Li, these results strongly prove that myostatin does not inhibit the proliferation of satellite cells.
Thirdly, to further confirm their theory that myostatin acts primarily through muscle cells, and not through satellite cells, scientists have bred mice with muscle cells devoid of myostatin receptors. If most of the myostatin receptors are on satellite cells, removing the receptors from muscle cells should not change the activity of myostatin. But the researchers observed a moderate but statistically significant increase in muscle mass, which once again proved that the muscle cells themselves are important receivers of myostatin signals.
Professor Lee notes that since his results do not provide any evidence that satellite cells are of primary importance for the molecular pathway of myostatin, even patients with reduced muscle mass due to suppression of the function of satellite cells are capable of some restoration of muscle tone with the help of drug therapy blocking the activity of myostatin.
We all lose muscle mass as we age, and the most common explanation for this is the loss of satellite cells.
"Is it possible to increase the muscle mass, mobility and independence of our aging population by blocking the myostatin pathway?" asks Professor Lee. "Our experiments on mice show that this strategy can really solve the problems associated with the loss of satellite cells."
Portal "Eternal youth" http://vechnayamolodost.ru15.10.2012