Myostatin (MSTN)is a class of growth factors that is a negative regulator of muscle growth. Myo means muscle, and statin means inhibitor. You may have heard of people with high cholesterol taking a “statin” to block high cholesterol. Well, think of myostatin as a muscle growth blocker.
SUMMARY OF MYOSTATIN-RELATED MUSCLE HYPERTROPHY HUMAN GENE RESPONSES TO ACUTE EXERCISE
- Both heavy and light weight to failure caused similar decreases in myostatin.
- Subjects performed either light weight (30% of a 1-RM) or heavy weight (80% of a 1-RM) to failure. 58 genes related to muscle growth were examined.
- Similar anabolic muscle gene expression was found regardless of the exercise bout (i.e., heavy or light).
Myostatin (MSTN)is a class of growth factors that is a negative regulator of muscle growth. Myo means muscle, and statin means inhibitor. You may have heard of people with high cholesterol taking a “statin” to block high cholesterol. Well, think of myostatin as a muscle growth blocker.
When MSTN levels are increased, there is a reduction in protein synthesis and loss of muscle mass. (Elliott et al., 2012) As we age, MSTN levels increase, which may explain why we lose muscle as we get older, but women have a greater increase in MSTN with age compared to men. (Bergen et al., 2015)
MYOSTATIN BLOCKS ANABOLIC SIGNALING PATHWAYS
MSTN blocks several anabolic pathways that are needed for muscle growth. MSTN has been found to block the mammalian target of rapamycin (i.e., mTOR) signaling pathway (i.e., mTOR inhibition blocks protein synthesis) and satellite cells. All these anabolic signaling pathways are important for muscle growth.
On the other hand, when MSTN levels decrease, increases in muscle mass occurs. A 4-week treatment of an anti-myostatin antibody significantly increased muscle mass and strength in young and old mice.(Camporez et al., 2016)
MYOSTATIN INHIBITION
The medical and athletic community has taken a big interest in pharmaceutical myostatin blockers, exercises that reduce myostatin, and supplements (i.e., myostatin-inhibiting supplements) demonstrating MSTN inhibition. Despite the marketing hype, there is no convincing evidence that myostatin inhibitor supplements are effective.(Santos et al., 2022)
LIFT HEAVY OR LIGHT WEIGHT? WHATS BEST FOR MYOSTATIN RELATED MUSCLE HYPERTROPHY
Certain breeds of animals are born with a natural MSTN deficiency, such as the Belgium blue cattle, mice, and deficient myostatin dogs, who demonstrate 2-3 times more muscle mass than their counterparts. (Aiello et al., 2018; Amthor et al., 2007) This mutation in the MSTN gene results in double muscling. (Shelton & Engvall, 2007)
Some people have a human myostatin mutation in which they are jacked and don’t even have to lift weights. A case study was published in the New England Journal of Medicine in which a boy was born with an MSTN deficiency and looked like a bodybuilder at birth!(Schuelke et al., 2004)
The Olympics committee is concerned about developing myostatin gene editing drugs because there is no way to test for this, unlike other performance-enhancing drugs such as testosterone, EPO, etc.(Brzeziańska et al., 2014)
MYOSTATIN AND RESISTANCE EXERCISE
MSTN is regulated by tension placed on the muscle. During injury, there is an increase in MSTN expression, and resistance exercise can decrease MSTN expression. Researchers found that if a healthy subject went from an active lifestyle of 13,054 steps per day to a sedentary lifestyle of 1,192 steps, the loss of activity decreased protein synthesis by 27% and increased the muscle-suppressing hormone MSTN. (Shad et al., 2019)
When you stop working out, you lose muscle, and there is an increase in MSTN expression. Following 90 days of weight lifting in young males, subjects lost muscle, and MSTN mRNA expression significantly increased by 56%, 79%, 107%, and 76% after 10, 30, 60, and 90 days in the detraining period.(Jespersen et al., 2011)
Studies have found that long-term resistance exercise reduces myostatin expression in muscles. (Kim et al., 2005) 9 weeks of resistance training decreased myostatin mRNA expression from vastus lateralis by 37% in all subjects. (Roth et al., 2003)
One would suspect that pro-bodybuilders have more muscle because they have some kind of myostatin deficiency; however, this is not the case. Most bodybuilders have similar levels of myostatin to control subjects. (Diel et al., 2010) MSTN is a part of the muscle growth process, but we can’t contribute all muscle growth to MSTN.
WHY IS MUSCLE GROWTH THE SAME WITH HEAVY AND LIGHT WEIGHT?
A new study published in Cells makes it easier to understand why light weight taken to failure and heavy weight taken to failure leads to similar increases in muscle gains. A similar article on Evidence Based Muscle discusses gene responses to heavy and light weights in women.
Researchers had young men perform two bouts of resistance exercises consisting of leg extensions and back squats. One bout with light weight consisting of 30% of a 1-RM to failure and another with a heavier weight consisting of 80% of a 1-RM. They had muscle biopsies taken after each bout and 3 and 6 hours later. They examined 58 genes regulating muscle growth, including myostatin.
SIMILAR GENE RESPONSES WITH HEAVY AND LIGHT WEIGHT TRAINING TO FAILURE
The researchers found that both bouts of exercise resulted in similar mRNA expression profiles and several myostatin-related mRNAs regardless of weight. Both bouts also similarly increased mTOR signaling pathways. Interestingly, both bouts acutely elevated follistatin protein levels (i.e., a protein that inhibits myostatin function) while not affecting myostatin protein levels. This study helps explain if there are similar gene expressions after heavy and light weight training; muscle growth will be similar as well.
REFERENCES
Aiello, D., Patel, K., & Lasagna, E. (2018). The myostatin gene: an overview of mechanisms of action and its relevance to livestock animals. Animal Genetics, 49(6), 505-519. https://doi.org/https://doi.org/10.1111/age.12696
Amthor, H., Macharia, R., Navarrete, R., Schuelke, M., Brown, S. C., Otto, A., Voit, T., Muntoni, F., Vrbóva, G., Partridge, T., Zammit, P., Bunger, L., & Patel, K. (2007). Lack of myostatin results in excessive muscle growth but impaired force generation. Proceedings of the National Academy of Sciences, 104(6), 1835-1840. https://doi.org/doi:10.1073/pnas.0604893104
Bergen, H. R., Farr, J. N., Vanderboom, P. M., Atkinson, E. J., White, T. A., Singh, R. J., Khosla, S., & LeBrasseur, N. K. (2015). Myostatin as a mediator of sarcopenia versus homeostatic regulator of muscle mass: insights using a new mass spectrometry-based assay. Skeletal Muscle, 5(1), 21. https://doi.org/10.1186/s13395-015-0047-5
Brzeziańska, E., Domańska, D., & Jegier, A. (2014). Gene doping in sport – perspectives and risks. Biology of Sport, 31(4), 251-259. https://doi.org/10.5604/20831862.1120931
Camporez, J. P., Petersen, M. C., Abudukadier, A., Moreira, G. V., Jurczak, M. J., Friedman, G., Haqq, C. M., Petersen, K. F., & Shulman, G. I. (2016). Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice. Proc Natl Acad Sci U S A, 113(8), 2212-2217. https://doi.org/10.1073/pnas.1525795113
Diel, P., Schiffer, T., Geisler, S., Hertrampf, T., Mosler, S., Schulz, S., Wintgens, K. F., & Adler, M. (2010). Analysis of the effects of androgens and training on myostatin propeptide and follistatin concentrations in blood and skeletal muscle using highly sensitive Immuno PCR. Molecular and Cellular Endocrinology, 330(1), 1-9. https://doi.org/https://doi.org/10.1016/j.mce.2010.08.015
Elliott, B., Renshaw, D., Getting, S., & Mackenzie, R. (2012). The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiol (Oxf), 205(3), 324-340. https://doi.org/10.1111/j.1748-1716.2012.02423.x
REFERENCES
Jespersen, J. G., Nedergaard, A., Andersen, L. L., Schjerling, P., & Andersen, J. L. (2011). Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining. Scand J Med Sci Sports, 21(2), 215-223. https://doi.org/10.1111/j.1600-0838.2009.01044.x
Kim, J. S., Cross, J. M., & Bamman, M. M. (2005). Impact of resistance loading on myostatin expression and cell cycle regulation in young and older men and women. Am J Physiol Endocrinol Metab, 288(6), E1110-1119. https://doi.org/10.1152/ajpendo.00464.2004
Roth, S. M., Martel, G. F., Ferrell, R. E., Metter, E. J., Hurley, B. F., & Rogers, M. A. (2003). Myostatin Gene Expression is Reduced in Humans with Heavy-Resistance Strength Training: A Brief Communication. Experimental Biology and Medicine, 228(6), 706-709. https://doi.org/10.1177/153537020322800609
Santos, H. O., Cerqueira, H. S., & Tinsley, G. M. (2022). The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype? Metabolites, 12(11). https://doi.org/10.3390/metabo12111146
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
Shad, B., Thompson, J., Holwerda, A., Stocks, B., Elhassan, Y., Philp, A., Loon, L., & Wallis, G. (2019). One Week of Step Reduction Lowers Myofibrillar Protein Synthesis Rates in Young Men. Medicine & Science in Sports & Exercise, 51, 2125-2134. https://doi.org/10.1249/MSS.0000000000002034
REFERENCES
Shelton, G. D., & Engvall, E. (2007). Gross muscle hypertrophy in whippet dogs is caused by a mutation in the myostatin gene. Neuromuscular Disorders, 17(9), 721-722. https://doi.org/10.1016/j.nmd.2007.06.008
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