The Real-Life Hercules Gene: Myostatin and Its Role in Bodybuilding

BY ANDRES ESCAMILLA

Working out is hard. Between finding the right time in your schedule, choosing the right exercises, and eating the right foods to promote proper muscle growth, the process can feel overwhelming. At times, you might even find yourself wishing you could build muscle without lifting a finger. For most, that’s just wishful thinking. For others, however, it’s their reality, and it’s all thanks to a deficiency in a single protein: myostatin. 

What is Myostatin?

Myostatin, encoded by the MSTN gene, is sometimes referred to as the “Hercules gene.” But why is that? Scientists Alexandra C. McPherron and Se-Jin Lee first discovered it in 1997 while researching unusually muscular cattle breeds, such as Belgian Blue and Piedmontese. 

They sequenced the MSTN gene and discovered that these cattle had a mutation in it. Ordinarily, the MSTN gene provides instructions for creating myostatin. Myostatin, as the scientists noted in their research, belongs to the TGF-β superfamily, which is a group of proteins that regulate cell growth. Myostatin’s function is to act as a negative regulator of muscle growth, a proverbial brake meant to limit both fiber number and fiber size in mammals. Due to the loss-of-function mutation these cattle had in the gene, myostatin was not being produced, resulting in their double-muscled appearance.

Of course, with this discovery came a new question: can this apply to humans?

Human Examples

Believe it or not, there is a precedent for humans naturally acquiring this mutation. In 2004, there was a case study of a German infant who was incredibly muscular and bulky, despite being only 4.5 years old and capable of carrying 3-kg dumbbells in horizontal suspension in each arm - far exceeding what a normal infant of his weight would typically be able to carry.

Additionally, Eddie Hall, a retired strongman known for his 500kg deadlifts in 2016, has claimed to have a myostatin deficiency. However, this is yet to be scientifically confirmed.

Tests and Understanding

It should be noted that myostatin gene mutations occur both naturally in populations and through manipulation in lab experiments.  In one study, there were tests done on mice in which scientists removed the MSTN gene, and noted that, as predicted, mice experienced increased muscular size. However, it was reported that despite the increased muscle mass, there was no proportional increase in strength that one might expect. Additionally, they relied more on quick bursts of strength, and their oxidative capacity was worse than typical mice. Essentially, making the myostatin-deficient mice worse in tasks that would require endurance, and better in activities that require quick bursts of strength. 

Where Does This Leave Us

So, does myostatin deserve the moniker of the “Hercules gene”? Results lean towards no. At first glance, a myostatin deficiency seems like a dream come true for any bodybuilder or athlete. Yet, as studies show, bigger, faster-growing muscles in this case do not necessarily mean better. In fact, they seem to tire out quicker and be less efficient. Certainly, for a strongman, this might be beneficial, but for a long-distance runner? They simply aren’t nearly as useful.

That said, the gene and protein aren’t a lost cause. Scientists are testing drugs that help inhibit myostatin to reduce its limiting in muscle growth to better treat muscle wasting conditions like muscular dystrophy and cachexia. While perhaps not the key to elevating us to mythical hero level strengths, the gene holds the potential to help and even save many lives. 

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McPherron, A. C., & Lee, S.-J. . (1997). Double muscling in cattle due to mutations in the myostatin gene. Proceedings of the National Academy of Sciences, 94(23), 12457–12461. https://doi.org/10.1073/pnas.94.23.12457

Bonnieu, A., Carnac, G., & Vernus, B. (2007). Myostatin in the Pathophysiology of Skeletal Muscle. Current Genomics, 8(7), 415–422. https://doi.org/10.2174/138920207783591672

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Schuelke, M., Wagner, K. R., Stolz, L. E., Hübner, C., Riebel, T., Kömen, W., Braun, T., Tobin, J. F., & Lee, S.-J. (2004). Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child. New England Journal of Medicine, 350(26), 2682–2688. https://doi.org/10.1056/nejmoa040933