The Secret To Building Muscle: Less Myostatin Equals More Muscle Mass

Myostatin means “stoppage of muscle growth.” Myostatin negatively regulates muscle growth and size of the muscular fiber during myogenesis (the formation of muscular tissue). It is the most important catabolic limiting factor of extreme muscular growth.

Scientists at the Johns Hopkins University isolated the protein in 1997. The earliest studies on animals born without the genes that code for myostatin production clearly showed that muscle growth is regulated by myostatin.  Extensive muscle hypertrophy was noticed in the animals.

Growth Differentiation Factor-8 (GDF-8) 

Myostatin, also called Growth Differentiation Factor-8 (GDF-8), is a protein that belongs to the family of secreted growth factors, TGF-β. Muscle cells are found to be extremely sensitive to this amino acid sequence. Several growth factors in this group mediate growth and differentiation during embryonic development. They also play a role in regeneration of muscle tissue in adults. Myostatin is unique among the family of growth factors in its expression in that it is restricted to skeletal muscle lineage. Myostatin is a protein encoded into the MSTN gene and people with mutations to the MSTN gene show significantly high levels of muscular mass and strength. 

Myostatin is produced in skeletal muscle cells, and circulates throughout the body, binding to muscle tissue. Inhibition of myostatin results in significantly larger muscle mass. During a workout, muscle cells are broken down and buildup must begin immediately to repair and grow the muscle cells. This process is affected by myostatin, which determines how large a muscle will grow. A significant increase of myostatin level in the blood will inhibit buildup of muscle mass, no matter how much one trains or exercises. Similarly, a significant decrease in the myostatin levels in the blood boosts muscle growth.

Role of myostatin in obesity

Myostatin can effect body metabolism due to its influence on skeletal muscle growth and active lean tissue, which in turn may subsequently play a role in the development of obesity and diabetes. Myostatin minimally effects metabolic activity of other tissues such as adipose tissue in the presence of optimal nutrition and produce only a slight contribution to the changes occurring in obesity. 

Myostatin as a therapeutic agent

Myostatin inhibitors may act as therapeutic agents for sarcopenia, or age-related muscular dystrophy in elderly people who are prone to injury that reduces their ability to lead a normal life. The aged population may benefit from increased muscle strength as myostatin levels have shown to decrease with age. In cachectic cancer patients who experience muscle wasting, increased muscle strength may improve quality of life, improve response to cancer treatment, and increase life span. Muscular dystrophies such as Duchenne’s muscular dystrophy may receive therapeutic benefit from increased skeletal muscle. Pharmacological inhibitors of myostatin may give therapeutic benefit to such debilitating muscular diseases.

Interactions between myostatin and hormones 

Myostatin levels and muscle size play a significant role because it might contribute to individual differences in muscularity or muscular atrophy in response to altered physical activity.

Numerous studies have shown that resistance training reduces myostatin expression in the 20 to 50 percent range. Recent studies focused on the interactions between myostatin and hormones such as growth hormone and testosterone suggesting that myostatin counteracts the anabolic effects of growth hormone and IGF-1.

The researchers suggested that anabolic effects resulting due to a combination of growth hormone and testosterone or anabolic steroids would be because of the steroid use. 

Another study that used humans as subjects found no relationship between body mass and myostatin in men, younger or older. However, when men are given testosterone, they found that myostatin increases after 56 days, and returns to the baseline after 20 weeks of testosterone treatment. Researchers suggest that myostatin rises with testosterone treatment due to the anabolic effects of testosterone that triggers the release of myostatin to stop excessive muscle growth, which is seen in younger men prone to muscle buildup compared to older men. In older men, the body reduces myostatin to counter loss of muscle.

Combined with large amounts of amino acids in the blood, insulin triggers muscle protein synthesis. Insulin on its own inhibits muscle protein breakdown and counters the catabolic effects of cortisol. Insulin resistance adversely affects these mechanisms. 

In extremely obese women, muscle cells produce a nearly threefold increase in myostatin. Insulin resistance boosts myostatin due to inhibited insulin activity, leading to cellular starvation. Loss of muscle mass is common in people with Type 2 diabetes.

Weight training and myostatin synthesis 

Regular weight training reduces myostatin activity in the body, which dictates the anabolic response necessary for muscle repair. The drop in myostatin levels sets off the process to repair muscles. This results in subsequent increase in muscle size in anticipation of another weight training session. The greater the level of workout, the lower the myostatin. Smaller decrease in myostatin will result in small changes in muscle growth, and bigger change will result in correspondingly bigger changes.

Myostatin behavior in humans is reportedly affected by race. Studies have reported that black people have higher muscular density, muscular mass, and strength compared to Caucasians. In a study that compared ethnic groups, it was found that black people showed gene activity that is consistent with lower myostatin than other ethnic groups. The group exhibited greater upper arm gains after a 12-week training.