Bodybuilding and Myostatin
Life Style

Author: Stefano Racca
Date: 03/12/2012

Description

Introduction

The bodybuiliding is the sport that through the use of weights and a specific diet has as its goal the growth of the muscle composition of the body, where the finality is aesthetic, not competitive. The aestetic taste pushes bodybuilders and various lovers of the discipline to train hard in order to increase body mass and muscle definition (obviously mantaining armony and body proportions, inspired by the criterions of the roman and greek classic sculptures, as a formule for a “perfect body”). The benefits of training carried on using weights generally goes beyond the bodybuilding: it is in fact the base of many other sports and of general well-being.

Physiology and metabolism

Skeletal (voluntary) muscle is divided into two broad types: slow twitch and fast twitch:
* Type I, slow twitch, or "red" muscle, is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity using fats or carbohydrates as fuel. Slow twitch fibers contract for long periods of time but with little force.
* Type II, fast twitch muscle, has two major subtypes (IIa and IIb) that vary in both contractile speed and force generated. Fast twitch fibers contract quickly and powerfully but fatigue very rapidly, sustaining only short, anaerobic bursts of activity before muscle contraction becomes painful. They contribute most to muscle strength and have greater potential for increase in mass. Type IIb is anaerobic, glycolytic, "white" muscle that is least dense in mitochondria and myoglobin.

It is known that the most sensitive fibers to growth are type IIa and IIb ones. However it seems that, depending on the type of training, you can get different hypertrophy effects: a high number of reps, in association with low weights and short rest (the so called “pumping” training) increases the rate of energetic substrates inside the fibrocells (+ glycogen, + lipids). This is called sarcoplasmic hypertrophy, while a high-weight, low-rep training increases mostly the rate of contractile proteins in the muscles: this is called myofibrillar hyperthophy. The most gifted individuals are those who genetically have a prevalence of type II fibers compared to type I fibers. It isn’t known yet if an overload training could lead to muscle hyperplasia.
The stimulation muscles receive when we lift a weight, causes a response in the organism, which through anabolic adaptation (anabolism) restores the involved tissues, and their glycogen deposits (giving hypertrophy), and recovers the substrates lost while training.
Moreover the strengh a muscle can unchain is proportional to its dimensions, number of recruited fibers (depending on the nervous system), length of bones and tendons.
Rest after training is the true step in which muscles and also tendons and connective tissue grow larger: this happens in the hours and days after the workout. In this fase the body needs to recover and to absorb nutrients useful for this operation: if in the meanwhile muscle is newly stimulated (a too close workout or an inadequate sleep as examples) or if there’s a lack of necessary substances, there’s the risk of overloading the organism, stressing it.

Diet

The fuel of the muscles is carbohydrates and the bricks that compose them are proteins. Natural bodybuilders have to watch out on the quantity and quality of carbs they introduce into their bodies with the diet due to the fact that sugars tend to change into fats if not consumed shortly after digestion. Many studies confirm that introducing a well balanced amount of proteins after a workout has benefits on growth instead. In normal conditions, an 80 kg athlete with 12% of fat mass has got 70,5 kg of lean body mass and must consume around 155g of proteins during the entire day. However it isn’t suggestable to exceed in the use of proteins due to the problems that could turn up: chronic tiredness, food allergies, digestive problems, kidney problems, joint problems and thus, paradoxically, also a tendency to lose weight and strength.

Dietary supplements and doping

There are many dietary supplements on the market, but only few of them show some efficacy. Of course it is necessary to moderate the dose, because their excess could be harmful (causing hyperazotaemia and kidney problems).

Creatine monohydrate

Creatine is a tripeptide normally synthesized by our body from amino acids primarily in the kidney and liver, which has an important role in the ATP-ADP cycle. This substance stimulates hypertrophy in muscle tissue (over 35% more) and improves strenght and speed.

Protein powder and BCAA

In the hours following a workout, the body is able to capture very effectively the substances it needs. An intake of protein powder (usually obtained from whey) or the so-called Branched-Chain Amino Acids (BCAA , ie leucine, isoleucine and valine) has positive effects on the efficacy of protein synthesis.

Anabolic steroids

These are steroids acting likewise to testosterone (stimulation of protein metabolism with an increase in strength and muscle mass and decreased fat mass). To obtain a dopant action it’s necessary to get much higher doses (up to 200 mg per day) compared to those suggested for therapeutic use. Steroids usually are taken in an eight-week cycle with a variety of ways. There are serious side effects such as aggressive behavior, inhibition of the synthesis of testosterone and increased level of estradiol, which can lead to severe metabolic disorders and male infertility. In women there is an effect of masculinization with menstrual irregularities, breast reduction, acne and increased hair growth. In general it is proven an increased frequency of myocardial infarction and stroke in people who have taken anabolic steroids.

Growth Hormone

Somatotropin (or Growth Hormone , GH) is a hormone that stimulates the growth of tissues and is responsible for the growth of organisms, intervening in the synthesis of proteins, in the metabolism of carbohydrates (as anti-insulin) and fats. It’s much more expensive than anabolic steroids. The therapeutic dose of GH is 0.01 to 0.06 mg/Kg, but there are cases of athletes who have assumed twentyfold the recommended quantity. Side effects: edema, paresthesia, arthralgia, myalgia, intracranial hypertension, headache, acute pancreatitis, and possibly diabetes, leukemia and acromegaly. It can also accelerate the growth of pre-existing tumors.

Since a few of years research is focusing on a drug that can inhibit the effect of myostatin, the enzyme that appears to limit muscle growth in living things.

Myostatin

The word "myostatin" come from the Ancient Greek μῦς (myo=muscle) and στατός (statin), which stand for "substance limiting the [growth of] muscle". Myostatin is an endogenous, negative regulator of muscle growth determining both muscle fiber number and size. The myostatin pathway is conserved across diverse species ranging from zebrafish to humans. Experimental models of muscle growth and regeneration have implicated myostatin as an important mediator of catabolic pathways in muscle cells. Inhibition of this pathway has emerged as a promising therapy for muscle wasting. Myostatin, also known as GDF8 (growth differentiation factor 8), belongs to the transforming growth factor-β superfamily of secreted growth and differentiation factors. In common with the TGF family, myostatin is synthesized as a precursor protein consisting of a signal sequence, an inactive/ inhibitory N-terminal propeptide region and an invariant Arg-X-X-Arg proteolytic cleavage site, followed by a C-terminal domain which dimerizes to form the active/mature molecule. After cleavage of the signal sequence and proteolytic processing, the mature C-terminal dimer remains associated with the propeptide via non-covalent forces creating a latent complex from which myostatin must be released to elicit its biological activity. This latent complex circulates in the blood and can be activated by acid treatment.

Inhibition of myostatin

Although the mechanism of activation of the latent myostatin complex remains to be determined, the bioavalaibility and the function of myostatin appear to be dependent of a network of protein interactions. Indeed, in addition to the propeptide, several other proteins have been identified as inhibitory binding proteins of myostatin. Through a number of yeast two-hybrid system experiments, four binding partners of myostatin (follistatin, hSGT, Titin cap and decorin) have been defined in muscle whereas two follistatin related proteins FLRG and GASP have be found to be complexed with myostatin in serum. These proteins are able to negatively regulate myostatin activation, secretion or receptor binding. The effects of these myostatin binding proteins are summarized in this table.

//In VitroAnimalHuman
Myostatin propeptideAntagonizes myostatin biological activity by inhibiting myostatin receptor bindingOverexpression of propeptide associated with increased muscle mass//
FLRGInhibits myostatin activity in signalling assays, maintains myostatin latencyOverexpression of FLRG associated with increased muscle mass//
GASP 1Inhibits myostatin activity in signalling assays, maintains myostatin latency ////
hSGTInhibits myostatin activity in signalling assays////
Titin-cap (telethonin)Myoblasts overexpressing titin-cap associated with increased myoblast proliferation, regulates myostatin secretion//Lack of functional Titin-cap protein is responsible for a rare limb girdle muscular Dystrophy type 2G
FollistatinInhibits myostatin receptor binding, antagonizes myostatin inhibition of myogenesis Overexpression of follistatin associated with increased muscle mass; Loss of Follistatin associated with reduced muscle mass//
Decorin Blocks the inhibitory effect of myostatin on proliferation of muscle cells////

Interestingly, three of these proteins, the myostatin propeptide, follistatin and FLRG have been shown to be capable of increasing muscle mass when expressed as a transgene in skeletal muscle of wild type mice; a phenotype comparable to those seen in myostatin knock-out mice. However, the increases in muscle mass in the follistatin transgenics are significantly greater than the increases in the myostatin null mice. Furthermore, when the follistatin transgene is combined with a myostatin null mutation, the two phenotypes appear additive as the increase in muscle mass is quadrupled. Such findings indicate that other ligands cooperate with myostatin to control muscle growth and underscore the need to determine the identity of such ligands to elaborate the most effective strategy for manipulating this signalling pathway. 

Myostatin and satellite cells

How does the myostatin signalling act on satellite cell activation, proliferation and differentiation? Recombinant myostatin is able to arrest the cell cycle at the G1 phase of cultured myoblasts. Growth and repair of skeletal muscle are carried out by a group of quiescent muscle stem cells known as satellite cells. In response to tissue damage or hypertrophic stimuli, these cells are activated and will proliferate and differentiate. However, a small proportion of these activated satellite cells does not differentiate, returns to quiescence to maintain the pool of satellite cells on the muscle fibers. Interestingly, myostatin has been proposed to be a key signalling molecule that signals the quiescence of satellite cells and their progeny, the myoblasts. Direct analysis of satellite cells in myostatin mutant mice has shown an increased number of satellite cells per single myofiber and a higher proportion of activated satellite cells compared to wild-type mice. In addition, satellite cells isolated from myostatin null mice proliferate and differentiate more rapidly than satellite cells isolated from wild-type mice. These results suggest that myostatin maintains satellite cells in a quiescent state and that during regeneration or muscle growth these muscle progenitor cells could be reactivated upon release from the inhibitory effect of myostatin. In line with this notion, several groups have attempted to elucidate the intervention of myostatin in muscle regeneration after injury or in degenerative diseases. It has been demonstrated that regeneration after injury in myostatin null muscle is improved compared to the wild-type controls. Recent evidences suggest that myostatin negatively regulates muscle regeneration not only by controlling satellite cell activation but also by regulating the migration of myoblasts and macrophages to the site of injury. Inhibition of myostatin in mdx mice that are known to have cycles of degeneration also reveals evidence for improved muscle regeneration in lack of myostatin.

Conclusion

In conclusion myostatin inhibition could be a good help for bodybuilders to grow. The point is: it is legit for a man to bypass with science what is imposed by nature? In this case I would say no: speaking about bodybuilding, using antibodies antimyostatin to inhibit his function is in my opinion a way to cheat, just like taking anabolic steroids. You wouldn’t need any training... if bodybuilding loses his spirit of sacrifice and the seeking of overcoming your own limits with your sweat, it loses everything it is worth of.

Bibliography

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2647158/pdf/CG-8-415.pdf
http://it.wikipedia.org/culturismo
http://en.wikipedia.org/bodybuilding
http://www.steroidology.com/human-growth-hormone-hgh-somatotropin
http://www.sciencedirect.com/science/article/pii/S1357272503000426
http://www.youtube.com

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