Skeletal muscle mass is regulated by two different AKT signaling pathways. The first pathway, known as mammalian target of rapamycin (mTOR) controls protein synthesis. The second pathway, known as forkhead box O (FOXO), controls protein degradation. Myostatin is a member of the factor-β superfamily that negatively regulates skeletal muscle growth. Specifically, “myostatin regulates the assembly of the translation pre-initiation complex in skeletal muscle cells… and decreases Akt phosphorylation and signals through FOXO transcription factors to increase expression of atrophy-related genes” (Rodriguez, et al., 2014). The inactivation of myostatin can therefore lead to muscle hypertrophy.
Naturally occurring mutations of the myostatin gene have caused increased muscle hypertrophy within animals. For example, the “bully” Whippet is a rare-breed of the English Whippet that carries a mutation in the myostatin gene. This mutation inhibits myostatin and allows for increased muscle mass that is not typical of the medium-sized canine. In addition, lab studies have shown that myostation mutations cause increased muscle growth in mice. When compared to wild-type, infant mice with mutations of the myostation gene have increased muscle fiber numbers and cross-sectional area (Rodriguez, et al., 2014). Therefore, the inactivation of myostatin through mutation does lead to increased hypertrophy. The question is then how myostatin inactivation can be used for muscle hypertrophy within humans.
One study within the “Journal of the International Society
of Sports Nutrition” establishes that novice athletes who took 10 grams and 30
grams of MYOX – a myostatin inhibitor supplement – had increased lean-muscle
mass when compared to the placebo group (Sharp, et al., 2014). However, the
study concludes that the increase in lean muscle mass within the experimental
groups could be caused by “neutral adaptions” of the novice subjects. In
addition, the use of creatine paired with consistent, resistance training also
decreases serum levels of myostatin (Saremi, et al., 2010). Therefore, the
inactivation of myostatin through supplementation does not seem to be of any
benefit to a highly trained individuals.
Whippet with myostatin mutation in comparison to a normal English Whippet (Genetic Engineering and Biotechnology News, 2018)
Refernces:
“Genetically Modified Dogs: Chinese Scientists Use CRISPR to Create Muscly Freaks.” Genetic Engineering and Biotechnology News, 26 Oct. 2018. https://www.genengnews.com/resources/videos/genetically-modified-dogs-chinese-scientists-use-crispr-to-create-muscly-freaks/.
Rodriguez,
J., Vernus, B., Chelh, I., Cassar-Malek, I., Gabillard, J. C., Sassi, A. H., .
. . Bonnieu, A. (2014). Myostatin and the skeletal muscle atrophy and
hypertrophy signaling pathways. Cellular and Molecular Life Sciences,71(22),
4361-4371.
Saremi,
A., Gharakhanloo, R., Sharghi, S., Gharaati, M., Larijani, B., & Omidfar,
K. (2010). Effects of Oral Creatine and Resistance Training on Serum Myostatin
and GASP-1. Molecular and Cellular
Endocrinology, 317(1-2), 25-30.
Sharp,
M., Lowery, R. P., Shields, K., Ormes, J., Mccleary, S. A., Rauch, J., . . .
Wilson, J. M. (2014). The Effects of a Myostatin Inhibitor on Lean Body mass, Strength,
and Power in Resistance Trained Males. Journal
of the International Society of Sports Nutrition, 11(Suppl 1).
As a collegiate athlete and fitness enthusiast, this is incredibly intriguing to me as well. Aiming more towards the athletics portion of things, muscle mass is incredibly important in playing and performing well for whatever sport you need. As I was doing some research however, it is imperative to know that with the muscle gain that comes from the mutation or reduction of myostatin doesn’t necessarily lead to movement/functional based improvements along with the increase in muscle mass (Amthor, 2007). The question would become what then to do to increase both muscle mass and actual force generation to improve performance-besides the use of straight steroids? This study could also become a question of ethics with myostatin mutations or medications that suppress the gene and whether they give an unnatural advantage, so on so forth.
ReplyDeleteAmthor, Helge., Macharia, Raymond., Navarrete, Roberto…Patel, Ketan. (2007). Lack of myostatin results in excessive muscle growth but impaired force generation. Proceedings of the National Academy of Sciences, 104 (6) 1835-1840; DOI: 10.1073/pnas.0604893104
Thanks for the reply Kyleigh. I am very interested in your statement that "the muscle gain that comes from the mutation or reduction of myostatin doesn’t necessarily lead to movement/functional based improvements along with the increase in muscle mass". From a force generation point-of-view this does not make sense. The classic physics equation states that force = mass * acceleration. Therefore, an increase in muscle mass should result in an increase in force generation - which can be applied to physical activity. However, the 2007 paper by Amthor et al. does provide credible evidence to your claim. The myostatin knock-out mice were weaker than the wild-type mice. As such, I am confused of why this occurred and would like to see further studies performed.
ReplyDelete