Muscle hypertrophy through a genetic lens

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Published on 22 July 2019
by Jean-Denis Thomson

Muscle hypertrophy through a genetic lens


It is a well-known and documented fact[1] that strength training promotes hypertrophy. However, there are some general rules to follow to facilitate the process:


  1. Get larger muscle mass.
  2. Use a load of 8–12 repetitions maximum (RM).
  3. Allow 30–90 seconds recovery time between each set.
  4. Perform a high number of sets per muscle group.


However, this is not a hard and fast rule and there is room for variations.


Changing the variables of your workout (sets, reps, time under tension, etc.) allows for more workout variations. Specifically, the hypertrophy range will have an impact on the natural secretion of androgens such as testosterone, IGF-1 (Insulin growth factor-1), and growth hormones. These three hormones promote muscle hypertrophy[2].


In addition, micro tearing caused by eccentric weight training stimulates an immune system response, signalling satellite-cell activation in pathways.[3] This process helps with muscle protein synthesis.


Despite the importance of these signalization pathways (hormone and immune), there is also a third path for understanding muscle hypertrophy: the kinase B (mammalian target of rapamycin (Akt/mTOR) signalling pathway.


Researchers Scott Gordon and Marcas Bamman are working to understand intercellular communication pathways to better explain myofibrillar hypertrophy.



Intercellular signalling pathways


Scott Gordon, (East Carolina University, Greenville, NC) has demonstrated that muscle hypertrophy is controlled, in part, by the signalling cascade beginning with the mTOR protein. Without this signalization, muscle hypertrophy would be “blocked,” meaning there would be no possible genetic translation.


The Akt/mTOR pathway is stimulated directly by mechanical stress induced by muscle contractions as well as through the IGF-1 (Fig. 1). The mTOR is activated by phosphorylation by means of ribosomal protein S6 kinase (p70S6K) and the eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1).


Ultimately, the Akt/mTOR’s role is to stimulate genetic translation. In other words, to produce a polypeptide chain to form muscle proteins.


Practical applications


The required muscle training for optimal hypertrophy results is not yet determined. According to Marcas Bamman (University of Alabama at Birmingham, AL), there are good, average, and bad responses for the same training regime. Volume, intensity, and training frequency all play a part in this phenomenon. Here are some guidelines:


The Akt/mTOR signalling pathway is driven by:

  • Weight training.
  • Replenishing glycogen (1.0–1.2 g/kg of carbohydrates 0–4 hours after the training)[4], inhibits adenosine monophosphate-activated protein kinase (AMPK).
  • Sufficient protein intake (15 g of protein less than 30 minutes after training)4 enables muscle synthesis.


Akt/mTOR pathway signalling inhibition is stimulated by:

  • Fasting.
  • Long-term aerobic training.
  • High-energy expenditure training.
  • Muscle glycogen deficits.
  • Insufficient protein intake.





To produce a muscle hypertrophy, hormone, immune, and genetic signalling pathways are stimulated by different types of training. Understanding these signalling pathways allows us to critically examine training prescriptions for muscle hypertrophy. Research is still needed to better understand the pros and cons of muscle hypertrophy.




Jean-Denis Thomson, B.Sc.

Training Department Director



[1] FLECK, S, J, KREAMER, W. Designing resistance programs, 2nd ed., 1997, p. 275

[2] Blair CREWTHER, Justin KEOGH, John CRONIN and Christian COOK, Possible Stimuli for Strength and Power Adaptation Acute Hormonal Responses, Sports Med, 2006, 36 (3), p. 215-238

[3] SPIERING BA, KRAEMER WJ, ANDERSON JM, ARMSTRONG LE, NINDL BC, VOLEK JS, MARESH CM. Resistance exercise biology; manipulation of resistance exercise programme variables determines the responses of cellular and molecular signalling pathways, Sports Med, 2008, 38 (7), pp. 527-540


[4] Debra WEIN, Post-Exercise Nutrition: Recommendations for Resistance and Endurance Training. NSCA’s performance training journal, vol. 7 number 3, p. 17–18


Jean-Denis Thomson
Kinesiologist, Training Department Director