Muscle growth

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Regulatory mechanisms of muscle growth and training

With genome, there is a certain muscle mass, which is deformed during childhood, youth, adulthood and during aging. Modifying factors include physical work, physical athletic training, nutrition, age, diseases and accidents. The latter include, for example, severe burn wounds. In those, muscle tissue may be lost almost completely but it can be re-established partially or even completely by medication, nutrition and muscle training.

Muscle tissue in children is about 25 percent of their weight, a normal healthy adult man about 45 and a woman about 35 percent. With aging, the relative proportion of muscle mass will reduce. There are a lot of individual differences. Skeletal muscles (striated muscles that are adherent to bone or skeletal cartilage) consist of about 18 percent of proteins and the remainder mostly of water, and also a little bit of carbohydrates and fat.

Skeletal muscles comprise about 50 to 75 percent of the entire body’s proteins. A small part of the skeletal muscle proteins are broken down and synthesized on a daily basis. It is estimated that in a week about half of skeletal muscle proteins are broken down and replaced by new ones. This is important to take into account for nutrition intake, for example. [1]

The principle of muscle growth

For adults, strength training is the most important muscle growth-producing method. The basic mechanism is that the amount of myofibrillar proteins (mainly actin and myosin proteins) increases in the muscle. These proteins become larger, and when they reach a certain size, they split in two so that the amount of proteins within the cell increases and requires more space. Thus the cell grows and becomes hypertrophied.

In addition, the stretching or lack of stretching has an effect on cell length. Stretching extends muscle cells, which is important for increasing of muscle speed and extension length. The increase of muscle cross-sectional area naturally effects the increase of muscle power.

Even exercising is unlikely to increase significantly the number of human muscle cells because their amount is strongly genetically regulated. When muscle cells grow the volume of muscle support tissue seems to grow around roughly the same proportion with myofibrillar proteins growth. When muscle cells grow, the protein synthesis capacity needs also increase in order to provide more proteins and growth.

According to present knowledge, a certain form of muscle stem cells i.e. satellite cells, help obtain more cell nuclei.  They are located in the space between the muscle cell membrane and the basal membrane that surrounds the muscle cells. Strength training will increase the amount of satellite cells which merge into muscle cells and deliver their nuclei to muscle tissue. In such a way protein synthesis capacity increases and allows for a more powerful muscle growth than before. [1]

Protein synthesis

At first the messenger RNA is formed, in accordance with the information contained in the cell nucleus, i.e. in the nucleus a so-called transcription takes place. After that, outside the nucleus, on the surface of ribosomes, a translation takes place when the transfer-RNA first brings amino acids as building material for the protein.

In a normal healthy human, protein decomposition and building are balanced. In diseases and different kinds of fasts, protein decomposition is greater than the construction i.e. synthesis. During strength training the protein synthesis is quite low but accelerates immediately after exercise and is active 24 to 48 hours after exercise. Protein nutrition before, during and after exercise has a great impact on protein synthesis activity.
Based on current research data, the primary limiting factor of protein synthesis is not the amount of amino acids delivered to a transfer RNA, but initiation of translation. The key elements for it are both the messenger RNA and transfer RNA and its methionine initiation amino acid merging and interaction with the ribosome and initiation factors of translation. The entire regulation network of protein synthesis is very wide [for example, 2, 3] and our present knowledge about it is constantly and rapidly increasing. It is currently (in 2010) one of the main research areas of exercise physiology.  [1]

Decomposition of proteins

Protein decomposition takes place in hydrolysis where the protein is decomposed to the original amino acids and their degradation products. For the entire decomposition, the proteolytic enzymes i.e. enzymes that degrade proteins, are essential factors.

Cell proteins degrade on a daily basis: new proteins are synthesized and defective ones repaired. In certain special situations, such as long-lasting endurance performances leading to exhaustion, and fasting, proteins are broken down and the amino acids are used for energy. For energy, primarily branched chain amino acids are used (leucine, isoleucine and valine).

In connection with hard and intensive strength exercise, the body breaks down large number of proteins. This in turn accelerates the protein synthesis even more and thus causes excessive muscle growth [4].

Anabolic i.e. constructive signals and catabolic i.e. decomposing signals have many of the same regulatory pathways and concerted impacts. For example, some anabolic regulation signals cause activation of protein synthesis, but the inhibition of degradation. Thus, the "economy and efficiency" will remain correct. The overall muscle growth, therefore, is determined by the difference between muscle proteins, in particular myofibrillar proteins, synthesis and degradation. [1]

Muscle hypertrophy and atrophy

Several factors related to strength exercises and nutrition have impacts on growth of the muscle or muscle deterioration i.e. muscle atrophy.  These factors are primarily muscle contraction and elongation forces, and muscle damages as well as the reactive molecules and their operation. Contributing factors include also the intracellular calcium regulation, liquid amount variation, energy requirements, oxygen content in the muscle, hormones, growth factors (both cytokines and their receptors), bloodstream changes and temperature.

The importance of hormone response during strength training for the muscle growth is controversial and likely to be much less than previously reported [e.g., 5]. A sufficient change in one or more variable results in the change or changes in the signal pathways, and thus the message will move within the network. The most common protein activity regulation mechanism in cells is the merging of a phosphate group to a protein (phosphorylation) or removal of a phosphate group from a protein (dephosphorylation).  These details in many muscle growth-related proteins are already fairly known.

Strength training and nutrition cause the activation of signal pathways in the latter’s beginning in various ways. At the end part, near the end of the protein synthesis, their impact methods are more similar. Muscle growth inhibition i.e. blocking is probably the result of many factors, both in animals and humans.

Myostatin is currently studied intensively. It is also known as GDF-8 and belongs to the TGF-ß cytokine protein class. It is known to have an influence in an endocrinal way i.e. by secretion from the tissues. Part of myostatin appears to be excreted into the bloodstream and is transported to tissues. However, it seems that myostatin is in human blood in very small quantities. 

Myostatin reduces muscle growth in adults by reducing the muscle protein synthesis which is important for muscle growth. The presence of myostatin can increase in the event of disease and/or immobilisation (i.e. immobilized limbs) related to reduction of muscle mass but its role in connection with strength training and nutrition has not been studied a lot.

In addition to myostatin, muscle growth-reducing factors include glucocorticoids and some other proteins degradation increasing and / or protein synthesis decreasing factors.  Myostatin inhibitors i.e. blockers, are under intensive research presently, especially in problems related to deterioration of muscle tissue.

Hypertrophic strength exercise is characterized by using a variety of exercise motions for the same muscle group.  The exercise often aims also to "isolate" exercised muscle and target the load only to a particular muscle or muscle group.

There is only a short rest of about two minutes or less, between the series which results in severe fatigue. There are many numbers of series and repetitions in the exercise. Usually the muscle tension is kept at a high and continuous level, without any relaxation between eccentric-concentric and concentric-eccentric contractions. [1]

Antti Mero
Professor in Exercise Physiology
Juha Hulmi
Doctor in Exercise Physiology
Department of Biology of Physical Activity, 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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