Everyone knows of someone who grows lean muscle more easily than others or someone who just appears incapable of growing significant amounts of lean muscle despite doing everything right. While there does appear to be a genetic basis to describe this process, it is not an excuse to accept that as a reason as to why one may not be able to grow muscle effectively. Why? Well simply because there is so much that can be done to effectively build lean muscle and actually modify genetic expression that if we simply assumed we are all genetically assigned unique muscle building machinery which predetermines our future then the majority of people would stop trying in the belief this is what’s holding them back and that it’s beyond their control. The reality is that while there is a genetic basis that governs lean muscle growth rates, it is unclear as to whether this is largely modified and altered over time or with changes in diet, supplements, medicines, hormones etc.
Furthermore, it also assumes that the following strategies have been correctly implemented and exhausted with minimal gains such as following correct protocols for:
Nutrition and importantly nutrient timing
While these four components may appear straight forward, there is significant variation in how people apply these components, and with Bro-Science taking the forefront in “evidence-based information” for gym goers there will always be a stack of scientific methods and principles people have not tried correctly and thus the room for improvements are still huge.
Now that Bro-Science can be eliminated as an excuse for trying everything possible and therefore claiming that one has reached their genetic potential, let’s explore the genetic differences contributing to individual differences in muscle growth rates (assuming all above-mentioned factors have been achieved).
It comes down to genetics but not in the way that we are necessarily born with a pre-determined growth potential as this is unclear and unlikely. Rather, its thought there is a dynamic regulation of gene expression that takes place during muscle protein synthesis (muscle repair and growth). Each gene contains DNA which carries the genetic code on for the production of new proteins. Genes are influenced by non-coding RNA such as microRNA’s (miRNA) which put simply influence the message coming from genes just before they are built into proteins, this is known as post-transcriptional regulation of genes (1).
This action on genes can also be of a silencing nature where gene messages or codes are supressed or “silenced” so the transcription (building process) is modified or myogenic in nature where they promote the muscle building process (2, 3). Resistance training leads to the activation of genes within the cell’s nucleus to build more muscle proteins however this process can be adversely influenced by miRNAs which ultimately result in less muscle protein synthesis taking place. MicroRNA’s were only discussed in the late 1990’s and since then it has only become apparent that those who respond highly to resistance training (build more muscle) and those who don’t (low responders, build less muscles) express different clusters of miRNA and thus exhibit a different degree of gene silencing action when it comes to muscle protein synthesis (4, 5).
What does this mean? To date it simply means there are genetic variabilities to explain the differences in muscle growth responses but it is unclear as to whether these microRNA clusters are modifiable. For example, does training experience influence the activity of these microRNA? Does nutrition and medicines influence their silencing effects? To touch on preliminary data which sheds light on such questions, a small randomised controlled trial examining the change in miRNA expression after the consumption of 10 grams of essential amino acids (EAA) reported a statically significant change in miRNA expression and muscle-growth related genes (myogenin, myostatin, myocyte enhancer factors etc.), within hours after the ingestion of EAA compared to placebo (6). Furthermore, training protocols and training experience also appear to modify the expression of miRNA profiles with examples drawn from experienced powerlifters expressing less inhibitory miRNAs and more myogenic miRNA profiles compared to matched untrained individuals (3, 7, 8). While not a perfect example to draw convincing conclusions from, it does shed light into an emerging topic which requires further well-designed trials on such a dynamic and complex response to exercise.
It is however fair to assume that while gene expression is known to be modifiable (just unclear to the practical specifics), understanding how miRNAs are regulated more specifically and what influences their activity is an area for further research in understanding the individual differences in lean muscle gain in response to exercise protocols.
In summary, to date the implementation of evidence-based muscle building strategies are the most effective strategies to incorporate into a muscle building program and while there appears to be genetic influences to the muscle building rate at a genetic level, it is quite possible these evidence-based strategies may in time continue to be shown to modify miRNA function.
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1. Keisuke e, Kunihiro e. Role of microRNAs in skeletal muscle hypertrophy. Frontiers in Physiology, Vol 4 (2014). 2014.
2. Bianchi M, Renzini A, Adamo S, Moresi V. Coordinated Actions of MicroRNAs with other Epigenetic Factors Regulate Skeletal Muscle Development and Adaptation. International journal of molecular sciences. 2017;18(4).
3. D'Souza RF, Bjornsen T, Zeng N, Aasen KMM, Raastad T, Cameron-Smith D, et al. MicroRNAs in Muscle: Characterizing the Powerlifter Phenotype. Frontiers in physiology. 2017;8:383.
4. Ogasawara R, Akimoto T, Umeno T, Sawada S, Hamaoka T, Fujita S. MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training. Physiological genomics. 2016;48(4):320-4.
5. Davidsen PK, Gallagher IJ, Hartman JW, Tarnopolsky MA, Dela F, Helge JW, et al. High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. Journal of applied physiology (Bethesda, Md : 1985). 2011;110(2):309-17.
6. Drummond MJ, Glynn EL, Fry CS, Dhanani S, Volpi E, Rasmussen BB. Essential amino acids increase microRNA-499, -208b, and -23a and downregulate myostatin and myocyte enhancer factor 2C mRNA expression in human skeletal muscle. The Journal of nutrition. 2009;139(12):2279-84.
7. Horak M, Zlamal F, Iliev R, Kucera J, Cacek J, Svobodova L, et al. Exercise-induced circulating microRNA changes in athletes in various training scenarios. PloS one. 2018;13(1):1-14.
8. Denham J, Gray A, Scott-Hamilton J, Hagstrom AD. Sprint Interval Training Decreases Circulating MicroRNAs Important for Muscle Development. International Journal of Sports Medicine. 2018;39(1):67.