Muscle growth

Regulatory mechanisms of muscle growth and training

June 14, 2019

By comparison with muscle atrophy, muscle growth is usually the more difficult one of the two to achieve. A significant factor behind this phenomenon is related to the great amount of energy required by the growth and maintenance of myocytes. Much to the annoyance of those trying to achieve muscle growth, the body has a number of mechanisms limiting rapid and abundant muscle growth. In addition to the best-known myostatin, these limiters of muscle growth include a number of other body proteins [11]. What is crucial to muscle growth capacity is the capacity of the myocytes to detect and regulate their own state, for instance, through sensors and signalling pathways. Examples of detection events include muscle activation during resistance training along with the following physiological changes, such as the rise in calcium ion levels in certain parts of the myocyte and the mechanical load. Moreover, resistance training involves metabolic loads and micro-damage in muscles, leading to changes, which the muscles have the capacity to detect. The individual characteristics of the loaded muscle and the intensity and duration of the loading type affect the magnitude of the aforementioned physiological responses. The myocytes seek to adapt to the challenge brought by the load and to develop their action in order to better respond to this challenge in the future [10].

Resistance training-induced muscle growth at the cellular level

In the process of muscle growth, proteins are built regularly in the long term and in numbers that are greater than the number of those that are broken down. Muscle protein synthesis builds proteins in the nuclei of the cells by linking amino acids together. This is often referred to as “muscle anabolism” and its regulation is important in the process of muscle growth. Growth in the breakdown of proteins will atrophy the muscles as in the case of many diseases or the mandatory rest brought about by an injury. The breakdown of proteins back into amino acids is referred to as “catabolism”. Normally, catabolism takes place in the body daily and, in the light of the newest information, a load-induced increase in protein breakdown is not a bad thing; rather, it may boost a post- practice increase in muscle protein synthesis [10, 9].

Increased muscle protein synthesis after practice alone will not grow muscle mass perpetually if the nuclei and the ribosomes acting as the protein synthesis engines fail to proliferate. The satellite cells located outside the myocytes have the capacity to increase the number of myocytes nuclei by sharing their nuclei with the myocytes. Thus, myocytes can grow by approximately 10–20% at the first stage of training without the proliferation of their nuclei [1]. The rate of protein synthesis is at its highest after practice or a protein-rich meal [9].

In practice, muscle growth involves muscle fibre hypertrophy. Without the growth and proliferation of the myocyte contraction machineries, called myofibrils, there is less muscle growth. Myofibrils grow mainly with the aid of structural proteins developed through protein synthesis. As the myocytes grow, the amount of water and connective tissues they hold generally grows as well [1, 6, 3]. Sometimes muscle tissue can grow even in ways other than through myocyte thickening. Growth in the length of the muscle fibres running diagonally in relation to the direction of force can affect muscle size, as can any change of muscle fibre angle in relation to the entire muscle. [10] Sometimes myocyte growth can also result from a particularly high rise in the volume of fluid and the number of non-contractile proteins. This is sometimes referred to as “sarcoplasmic hypertrophy” [5]. However, much more research on this topic is needed before its significance can be understood better.

The mechanical and metabolic loads on muscles

During resistance practice, the muscles are subjected to mechanical load, which refers to the active and passive forces exerted on the muscle. Myocytes contain proteins that sense mechanical load and activate various signalling pathways accordingly. Possibly one of the best known force-sensing proteins is filamin-C, which is located in the myofibril sarcomeres near the Z-discs. From this position, filamin-C can sense the forces produced by the muscles (actomyosin interaction). The muscles also have a number of other force-sensing proteins, but their action is little known [10]. Even today, the cellular level mechanism that triggers resistance training-induced muscle growth in the early stages of training—or, in the case of people who have trained for longer, when approaching one’s maximum potential—is not known yet. A metabolic stimulus can act as a muscle growth stimulus as well [8]. Hundreds of metabolic changes take place in the muscles and their significance for muscle size growth is still poorly understood. Examples of these include local oxygen deprivation related to energy consumption and production, the energy situation (involving things like the adenosine triphosphate/adenosine monophosphate (ATP/AMP) ratio or a decrease in creatine phosphate and glycogen), as well as the release of amino acids into the myocytes through protein breakdown, and changes in the levels of free radicals or other muscle metabolites, involving cellular swelling [10, 8]. Therefore, the metabolic load has an indirect effect on muscle growth although, according to present knowledge, the mechanical load is the muscle growth trigger of comparatively greater significance [10]. In practical resistance training, training that is followed through to its completion at submaximal loads accumulates metabolites and increases other fatigue-inducing factors so that at the end of the series the fast myocytes have to produce force as well, thereby being subjected to mechanical load. Otherwise, the series will end prematurely. Consequently, the fast myocytes, which are often also sensitive to growth, can grow at lower loads than what scientists have understood before [10].

Micro-damage to muscles and post-training muscle soreness

Muscle growth also takes place through inflammation processes and changes in the growth factor levels, both of which are related to the repair of training-induced micro-damage to muscles. In resistance training, micro-damage develops as a consequence of both the mechanical load (in particular, stretching load) on the muscle tissues and the metabolic changes. If muscle soreness is delayed, this condition is referred to as “Delayed Onset Muscle Soreness” (DOMS). After hard practice, muscle soreness will generally appear within 24–48 hours and it should not be confused with muscle injuries or fatigue pain experienced during training. Muscle soreness develops from exercise-induced micro-damage to the muscle or the membrane structures surrounding it. Swelling, the accumulation of metabolic products, and any inflammatory reaction will increase muscle soreness. Muscle soreness is generally stronger if the resistance training is carried out at high intensity for a prolonged period. Overemphasis on the eccentric (braking) stage and the lack of familiarity with the movement to be carried out are factors, which increase muscle soreness after practice [10, 8,]. A number of mechanisms are related to muscle growth, so mere muscle soreness after practice will not say very much about the developmental aspects of the practice. However, an international research group report [10] speculates that practice that induces micro-damage may boost the number of muscle satellite cells and thus provide beneficial further aid when maximizing muscle growth. Once again, however, more research is needed.

Muscle growth is regulated by signal transduction pathways

The regulation of muscle growth in itself is a complex process; it certainly involves more than the biology of a single molecule. As a consequence of loads and meals, the muscles sense changes that trigger muscle growth through a variety of signal transduction pathways. The amount of muscle protein is regulated by these pathways, which are formed of molecules interacting with one another. The most important pathway is called mammalian target of rapamycin (mTOR) and it consists of a number of multi-protein complexes, the significance of which is not understood yet. [7] After resistance practice or a protein-rich meal, mTOR is activated and accelerates protein synthesis by activating a number of other proteins [4]. Other examples of muscle growth regulators in resistance training include the testosterone androgen receptor and the signalling related to it, the c-Jun N-terminal kinase/smad (JNK/SMAD) signalling axis, the calcium dependent pathway, and possibly the Hippo pathway, as well as PGC­1­GRP56 and insulin-like Growth Factor-1/mechano-growth factor (IGF1/MGF) insulin signalling.

Muscle growth is individual-specific

Muscle growth, like many other changes taking place in our bodies, is affected by factors that are specific to the individual. In some people, muscle growth may be minimal despite a well-planned training program that works well on average. In others, the development may be surprisingly strong [2]. These differences are affected by the workout quality, nutriments and sleep, but also genetic factors. The mechanisms explaining the individual-specific nature of the resistance training response are not known currently, however. The individual-specific factors related to muscle growth should be studied more so that resistance training could be optimized better on a case-by-case basis.


Antti Mero
Professor in Exercise Physiology

Juha Hulmi
Doctor of Sport Sciences

Faculty of Sport and Health Sciences
University of Jyväskylä

Updated by

Juha Hulmi
Doctor of Sports Sciences
Associate professor in Exercise Physiology
University of Jyväskylä

[1] Hulmi (2007): Lihaskasvu ja sen säätelymekanismit. Teoksessa Alaranta, Hulmi, Mikkonen, Rossi & Mero: Lääkkeet ja lisäravinteet urheilussa – suorituskykyyn ja kehon koostumukseen vaikuttavat aineet. Nutrimed Oy.

[2] Proud (2007): Signaling to translation: how signal transduction pathways control the protein synthetic machinery. Biochemical  Journal 403: 217–234.

[3] Drummond, Dreyer, Fry, Glynn & Rasmussen (2009): Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. Journal of Applied Physiology 106: 1374–1384.

[4] Nader ym. (2005): Molecular determinants of skeletal muscle mass: getting the ”AKT” together. International Journal of Biochemistry & Cell Biology 37: 1985–1996.

[5] West ym. (2009): Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signaling in young men. Journal of Physiology 2009. Julkaistu verkossa ennen painamista (7.9.2009). Digitaalinen tunniste (The Digital Object Identifier DOI ®) 10.1113/jphysiol.2009.177220.

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