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Mighty Mouse: Understanding Myostatin

  • 9/17/2012 10:06:00 AM
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Mighty Mouse: Understanding Myostatin

Kevin Shimkus, B.S.

As is well known, physical gains become slower and more difficult to achieve as athletes reach a more elite status.  For those involved in strength- and power-based sports, improvements in strength and mass eventually plateau, and even rigorous workout and nutritional prescriptions may yield only minimal increases.  So it is little surprise that many in the athletic world are starting to pay more attention to some very special mice.

                The myostatin gene (MSTN), found in skeletal muscle, encodes for a protein, also called myostatin, which limits muscle growth.  Myostatin reduces protein synthesis and activates muscle protein breakdown, contributing to muscle regulation in two distinctly different ways.  But mice selectively bred to inhibit this gene have roughly twice as much muscle mass (with no additional physical activity) as normal mice, and this growth is due to both an increase in muscle fiber size and fiber number.  Work in cell culture has shown that when MSTN is overexpressed, muscle cells have reduced protein synthesis and smaller fibers.  Even mice that fully expressed MSTN at birth but underwent inhibition of the protein as adults displayed significant growth in muscle mass.  A study published in 2007 actually achieved quadrupling of muscle mass in mice with further manipulations to the myostatin signaling pathways (Fig. 1, Lee 2007).  These animals have functioned completely normally, with no major health concerns due to the inhibition of the protein, and demonstrate reduced fat mass compared to normal controls.  Similar results have been found in dogs, cattle, and sheep, and even in a case of a human child with myostatin deficiency and increased muscle gains.  The only known application of a myostatin deficiency in athletic competitions is found in dog racing, as whippets born with a loss-of-function MSTN display a competitive advantage. 

While athletes cannot undergo genetic manipulations or selective breeding, a scientific understanding of this gene and the effects of its related protein can assist those trying to improve or maintain muscle.  Clinical research applies the animal findings to humans to improve the quality of life for those facing muscle-compromising diseases, such as muscular dystrophy or cancer.  Researchers are currently focusing on treatments to reduce, even temporarily, myostatin levels to create a muscle-building environment.  In one study, mice given a myostatin-inhibitor were subjected to a leg cast for 14 or 21 days, and the animals given the anti-myostatin drug had less muscle mass loss than animals not given the drug.  Another study with myostatin inhibitors displayed muscle mass increases in mice in as little as two weeks.  Research in healthy individuals showed an increase in human MSTN expression with unloading (not using the muscles), as seen with inactivity, bedrest, or spaceflight, and – conversely --myostatin protein and its role in limiting muscle mass reduced with heavy resistance training.  Myostatin gene expression seems to be higher in young men when compared to women or older individuals, but men also exhibited the greatest reductions following resistance training.  Therefore, young men may be the group most likely to benefit from myostatin-reducing actions or therapies.  This could be one of the main reasons that young men display greater muscle gains than other groups. 

There is a definite need for research to better understand myostatin, but those in the sports field must take caution: to date, no myostatin-reducing products have been approved for the public. While anti-myostatin products are being marketed, they carry little to no scientific backing and probably high risk.  As human-approved agents become available, many sports committees will most likely view these products as unfair gains and they will be prohibited.  So while the allure of 400% gains in muscle mass may currently elude sports athletes and bodybuilders, the knowledge gained from these research efforts can still be applied to both the clinical and sports fields, helping to build muscle in those afflicted by disease or injury as well as impact healthy athletes striving to build more muscle.





Additional Readings:

  1. Gustafsson, T., T. Osterlund, et al. (2010). "Effects of 3 days unloading on molecular regulators of muscle size in humans." Journal of Applied Physiology 109(3): 721-727.
  2. Lee, S.-J. (2007). "Quadrupling Muscle Mass in Mice by Targeting TGF-ß Signaling Pathways." PLoS ONE 2(8): e789.
  3. Murphy, K. T., V. Cobani, et al. (2011). "Acute antibody-directed myostatin inhibition attenuates disuse muscle atrophy and weakness in mice." J Appl Physiol 110(4): 1065-1072.
  4. Roth, S. M., G. F. Martel, et al. (2003). "Myostatin Gene Expression Is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication." Experimental Biology and Medicine 228(6): 706-709.



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