It’s readily apparent that specific traits are passed down to us by our parents (and their parents and so forth). As fortune would have it, our capacity to build muscle (and stay lean) are very much inherited traits. Does this mean that if your parents aren’t jacked and shredded you can’t be a successful bodybuilder? Absolutely not.

Rather, this means that some people simply have a greater propensity to stay lean and pack on muscle mass; sadly, not everybody has the genetic makeup of a world-class bodybuilder. That’s life, though. Not everybody can be a 7-foot NBA player or an Olympic athlete either. Genetics are pretty much like the lottery of biology. You have to work with what you’re given.

The good news is that the vast majority of people can build a substantial amount of muscle with the right work ethic and consistency in terms of diet and training. Remember, hard work beats talent when talent doesn’t work hard.

Naturally, you’re probably doubting the veracity of the claim that your muscle-building potential is genetically determined. However, science says it very much it is. Read on to learn why that is, and more pertinently, can it be altered?

Is Your Muscle Growth Potential Limited By Your Genes?

Recent research reveals some highly intriguing information about the hypertrophic (growth) potential among humans being regulated by types of noncoding micro-ribonucleic acids (miRNAs).1 miRNAs are genetic regulators capable of blocking protein-coding genes, acting predominantly in the brain and muscle tissue.

We all have a mix of miRNA types and they are actively involved in cellular differentiation and metabolism. Research indicates that specific types of miRNAs differ between highly hypertrophic and lowly hypertrophic individuals. In non-nerd lingo, this means resistance exercise increases muscle mass greatly in some while less so in others.

Specific to muscle tissue, it turns out that particular miRNAs are significant regulators of muscle protein expression. The present study reveals differences between humans in the abundance of specific types of miRNAs which account for variances in how much muscle accrual one will experience from resistance exercise. It begs the question (which remains scientifically unanswered), can we alter miRNA abundance (safely)? If so, how? It may be as simple as figuring out what the miRNA does and introducing that "does" in abundance.

Perhaps gene doping would be one way to modulate the abundance of miRNA in muscle tissue? It’s simultaneously intriguing and disconcerting to think about these potentials because it would drastically shift bodybuilding paradigms. Everyone would have the potential to be the next Ronnie Coleman or Phil Heath. In my opinion, that wouldn’t be a good thing for the sport; we would start to take such impressive physiques for granted. As sucky as it is that we can’t all be Mr. or Ms. Olympia, that’s what makes it all the more impressive (if you’re a fan of bodybuilding).

Speculative digressions aside, there’s a bit more science to consider on this topic.

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Genetics of Muscle Hypertrophy Response in Humans

If you’re not familiar with genetic science, here’s a few terms to know before you read further:

  • Phenotype - Denotes the observable characteristics (physical and physiological) of an organism, which is influenced by the environment and genome.
  • Gene Expression - The process by which possession of a gene leads to the appearance in the phenotype of the corresponding character.
  • Translation - The process of decoding a messenger RNA (mRNA) into a polypeptide/amino acid sequence.
  • Transcription - The process by which DNA is copied/transcribed to mRNA, which carries the information needed for protein synthesis.

Generally, changes in skeletal muscle phenotype after consistent progressive resistance training consist of gains in strength, increases in lean body mass (LBM) and muscle fiber hypertrophy, and improved insulin sensitivity. Thus, the significance of a person's ability to adapt to resistance training may eventually influence numerous risk factors for conditions like sarcopenia and may likewise be essential for long-term metabolic health by lowering insulin resistance. (After all, being able to build a decent amount of muscle is somewhat conducive to longevity).

The study referred to initially herein showed for the very first time that resistance training-induced growth of skeletal muscle tissue in humans is connected with specific modifications in miRNA quantities. The distinctions in miRNA levels after consistent resistance training in low- and high-responders hint that miRNAs are responsible (in part) for modulating the translation of crucial gene complexes that control human skeletal muscle development.

Interestingly, the expression levels of miR-133a/b and miR-1, which were previously connected to short-term rodent muscle hypertrophy, were unchanged after a 12-week resistance training program in humans.2 As such, the present study is somewhat of a landmark in that it analyzed human muscle (via biopsy).

Variability of Muscle Hypertrophy in Humans

(Note: If you’re not interested in the deeper science behind the topic at hand, a layman’s summary is available at the end of the article.)

Humans indubitably show large variability in their responsiveness to progressive resistance training. Aspects such as age, gender, diet, exercise type/volume, and others are commonly postulated to impact the degree of muscle one can accrue.

Surprisingly, previous research studies, in addition to the study on which this article is based, showed significant variation in the degree of resistance training adaptation (even when these key variables are controlled for).3 Hence, more data is needed to help pinpoint which factors substantially affect human variation in muscular growth following resistance training.

It’s been demonstrated that during resistance training, muscle hypertrophy can be limited by the available muscle satellite cells.4 Further research shows that mTORC1 signaling is increased for 24-36 hours after intense resistance training, while modulation of S6K1 was correlated positively with increased muscle fiber size after 16 weeks of resistance training.5

If you’re a little lost at this point, just know that mTORC1 and S6K1 are proteins that regulate cell physiology, and that certain miRNAs to be discussed target these proteins.

Thus, the researchers in the this study tried to anticipate the significance of the modulation of miRNA expression in the context of the degree of real-world hypertrophy observed. This same team of researchers recently showed that in human skeletal muscle, miRNA modifications appear to work in a combinatorial manner to alter valid protein targets controlling muscle growth.6

The chosen panel of miRNAs belong to 14 independent families of miRNA. Hence, it might be anticipated that they collectively comprise a large and varied set of gene networks.

The researchers also profiled some pertinent members of the gene networks targeted by the cumulative effect of miR-378, miR-29a, miR-26a, and miR-451 modulation to further understand if these genes were over- or under-regulated in relation to muscle hypertrophy. Decrease of miRNA expression might make up for the loss of transcription activation of a targeted gene by permitting more effective protein synthesis from mRNA (remember: miRNAs effectively “silence” genes by blocking protein production).

Therefore, lower mRNA responses might be secondary to reduced miRNA expression.

Notably, under in vivo settings, the researchers found no evidence suggesting that these miRNAs target the net breakdown of mRNA; rather, they are believed to regulate translation.

miRNA Modifications in Relation to Muscle Hypertrophy

It was formerly thought that miRNAs largely regulate transcription abundance in higher organisms; this theory is largely based on in vitro analysis, however. The present analysis suggests that transcription supplying mRNA to protein synthesis machinery might be "tuned" by the abundance of miRNA (managing how efficiently the mRNA is used as a template for protein synthesis).

The present study showed the four miRNAs (miR-378, miR-29a, miR-26a, and miR-451) changed with resistance training correctly determined signal transduction paths for muscle hypertrophy.

Very limited past research has addressed miRNA expression in response to dynamic changes in lean body mass. In contrast to the previously mentioned finding of the same expression of miR-1 and miR-133a after 12 weeks of resistance training in humans, a more recent study showed that the expression of these two muscle-specific miRNAs was decreased by nearly 50% following seven days of “heavy” training overload.7

This variation might suggest that these two muscle-specific miRNAs may be modulated during only the initial phases of skeletal muscle overload. These findings could indicate that this preliminary response subsides when the resistance training duration is prolonged and does not appear to be linked to the level of physiological change.

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Key Findings

21 miRNA were analyzed; four showed differential expression in response to resistance training. Decreases of miR-378, miR-26a, and miR-29a and increase of miR-451 were found only in individuals who failed to exhibit a significant hypertrophy response to resistance training for 12 weeks. Naturally, you might wonder just how significant these genetic differences are when put into real-world context.

In short: Quite significant. In fact, upwards of 12 lbs difference in added lean body mass between those who responded highly and lowly in this 12-week resistance training study.

IGF-1 mRNA expression was significantly lower in the same group of low responders compared to the those exhibiting a high response to resistance training.

Furthermore, miR-1 is downregulated by the combination of acute resistance exercise and proper amino acid intake. Given these data, it’s postulated that miR-378, miR-29a, miR-26a, and miR-451 play a central role in the context of muscular adaptation and aging.

Moreover, this same study offers added evidence for the transcriptional differences between high and low responders, which, together with the miRNA information, shows that subjects with a poor ability to accumulate skeletal muscle despite consistent resistance training have a peculiar response on the molecular level.

Layman’s Takeaway

  • mTORC1 and S6K1 are proteins that regulate cell physiology and growth; miR-378, miR-29a, miR-26a, and miR-451 appear to target the mTOR pathway (which has downstream impact on S6K1 and ultimately muscle anabolism).
  • IGF-1 mRNA levels are modulated by these same four miRNAs, and individuals who exhibit low response to resistance training had significantly less IGF-1 mRNA compared to high responders.
  • Consuming proper essential amino acids - like PHARMGRADE - was shown to favorably alter miR-1 expression in combination with resistance training.

If there’s one thing you should take away from this article, it’s that your genetics do very much control how much muscle you can build. By the same token, miRNAs are implicated in the process of fat loss and lipid metabolism (which would be interesting for a future article). Basically, your ability to get lean and pack on lean body mass are controlled (to a degree) by your genetics.

Is this article trying to give you an excuse to be complacent with your current physique and write-off the rest as “crappy genetics”? Not at all. Rather, it’s shedding light on the veritable difference among humans to respond poorly or efficiently to exercise and proper diet based on their genetics.

Ultimately, you have to do your best with the hand that life deals you. For some people, this means working your tail off to put on 10 lbs of muscle in three years; for others, this means working your tail off for three months to put on that same 10 lbs of muscle. (And those numbers are not arbitrary based on the research covered herein.)

You can’t always control your circumstances, but you can control how you respond. Train hard, eat right, and let the chips fall where they may. Bodybuilding is a contest with yourself, after all. Be better than yesterday and don’t worry what everyone else looks like or how they might be able to build muscle quicker than you can. The more pertinent question is: “What are you going to do about it?”

References

  1. Davidsen, P. K., Gallagher, I. J., Hartman, J. W., Tarnopolsky, M. A., Dela, F., Helge, J. W., ... & Phillips, S. M. (2010). High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression. Journal of applied physiology, 110(2), 309-317.
  2. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38: 228 – 233, 2006. 10.
  3. Hubal MJ, Gordish-Dressman H, Thompson PD, Price TB, Hoffman EP, Angelopoulos TJ, Gordon PM, Moyna NM, Pescatello LS, Visich PS, Zoeller RF, Seip RL, Clarkson PM. Variability in muscle size and strength gain after unilateral resistance training. Med Sci Sports Exerc 37: 964 –972, 2005. 25.
  4. Petrella JK, Kim JS, Mayhew DL, Cross JM, Bamman MM. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol 104: 1736 –1742, 2008
  5. Terzis G, Georgiadis G, Stratakos G, Vogiatzis I, Kavouras S, Manta P, Mascher H, Blomstrand E. Resistance exercise-induced increase in muscle mass correlates with p70 S6 kinase phosphorylation in human subjects. Eur J Appl Physiol 102: 145–152, 2008.
  6. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 455: 58 –63, 2008. 40.
  7. Drummond MJ, McCarthy JJ, Fry CS, Esser KA, Rasmussen BB. Aging differentially affects human skeletal muscle microRNA expression at rest and after an anabolic stimulus of resistance exercise and essential amino acids. Am J Physiol Endocrinol Metab 295: E1333–E1340, 2008.