Muscle: The Myostatin Connection

- M. Doug McGuff, M.D.

At Ultimate Exercise, my exercise-training facility, we train all our clients with essentially the same routine. Whether you are male or female, young or old, strong or frail we train you on the same basic movements as we do any other client. Muscle and joint function is the same in all humans and thus, the exercises that track muscle and joint function will be the same for just about anyone. Over time the length and frequency of the routines will be different because different people have differing recovery abilities. However, everyone pretty much starts out the same. As clients first start this routine we are always faced with some early concerns.

Despite the fact that everyone starts out on the same routine, we find that the early concerns fall into categories that are clearly male or female. Females are universally concerned that our routine and techniques will make them too muscular and bulky. Males are universally concerned that our routine and techniques will not make them muscular and bulky enough. After about 12 weeks of training we find that about 5% of females feel they have become too muscular in some area of their body. Paradoxically, we find that about 75% of the male clients feel that they are not getting as big and as muscular as they would like. What accounts for this? It seems that females are for the most part pleasantly surprised that they did not grow too much muscle and that males are for the most part disappointed that they did not get as big as they would like. It seems that packing on slabs of muscle is relatively rare for both males and females. Why is this so?

The Genetics of Muscle Growth

Remember that we have said that muscle is very metabolically expensive tissue. It takes 50-100 calories a day to keep an extra pound of muscle alive. Synthesizing a pound of contractile tissue through DNA transcription is also expensive. Muscle is expensive to make and expensive to sustain. Your body will not make muscle unless it has a really good reason to need the extra strength that this tissue can supply. This is why it takes a severe exercise stimulus to cause muscle growth. Continues application of the exercise stimulus does not result in never-ending muscle growth. It seems there is some sort of point of diminishing returns.

Here we see that economics rears its head again. The law of diminishing marginal utility comes into play again. Each successive strength increase is less valuable than the ones that preceeded it. This is because your body has to weigh its need for additional strength against other needs. Probably one of the biggest needs your body has to weigh against its need for yet another spurt of muscle growth is its need for thermoregulation. Human beings are homeotherms; we must maintain a stable body temperature of around 98.6 degrees farenheit in order to function optimally. How does this relate to muscle? Well, we produce heat in proportion to our body mass (particularly our lean muscle mass), and we dissipate heat in proportion to our body surface area. If you have more muscle growth you will produce an increase in volume that is roughly 3 times greater than the concommitant increase in body surface area. When this happens your cooling efficiency drops. Thus one of the main reasons for your body to limit muscle growth is to preserve a stable body temperature.

Another reason to limit muscle growth is that there is decreasing mechanical efficiency as more and more muscle growth occurs. Picture a muscle as being shaped like a football with a tendon on either end. The tendon is the cable that the muscle cells pull on to move the joints. The muscle cells produce pull along the long axis of the tendon. Early in the growth process, growth is maximized centrally, in the fibers that have the greates mechanical advantage when pulling on the tendon. Growth at later stages proceeds towards the outer fibers. Strength increases in these fibers have less of an impact on functional strength because these fibers pull at the tendon from an angle and thus have a mechanical disadvantage. Sometime during the growth process the mechanical disadvantage becomes so great that it is no longer worth the added weight and metabolic expense to produce additional muscle.

Ultimately, the organism seems to weigh its need for a level of strength that it may use very rarely against the expense of carrying around and supporting this extra tissue. It is sort of like having a sports car that can go 190 mph when you live in a large city where the traffic never allows you to go faster than 35 mph. There are probably many other factors that come into play, but there clearly seems to be some sort of regulatory system that regulates muscle growth.

The Myostatin Connection

We had long suspected a genetic regulation of muscle growth potential, but none of the people in the exercise field had the capability of figuring this out. Typical of many of the biggest discoveries in science, our answer came from well outside our own field. The answer to the genetic regulation of muscle growth came from the field of agriculture.

In Belgium there is not much in the way of sprawling ranch-land. Cattle farmers there had to find a way to get more bang for their buck in order to stay economically viable. Over the years these ranchers selectively breeded for more muscular cattle. Ultimately, they were able to produce an animal that had 2 to 3 times the muscle mass of a normal cow. The animal is called a Belgian Blue. See the photo below.

The economic impact of producing 2 to 3 times as much marketable meat on a single animal was obvious and resulted in a race to discover the genetics underlying this phenomenon. A scientist named Michel Georges at the University of Liege at Belgium was able to isolate a gene called GDF-8 which encoded for a protein called myostatin. Myostatin is a protein that sends a signal that determines how large a muscle can become. When a muscle approaches the limits of its size, myostatin stops any further size increases. Dr. Georges was able to show that the Belgian Blue cattle had a deletion of the GDF-8 gene that is responsible for myostatin production. As a consequence, these animals had no regulation of their muscle growth and thus became very muscular. Realize that this occurred with no exercise or special diet. In the same way that an albino lacks the gene that encodes for melanin (which produces skin pigment), these animals lacked the gene that encodes for myostatin (which limits muscle growth).

Shortly after this discovery Drs. Sejin Lee and Alexandra McPherron at Johns Hopkins University discovered a similar mutation in Piedmontese Cattle. Lee and McPherron wanted to prove that the gene deletion was not just a chance association. To prove that myostatin regulated muscle growth, they need to knock out the gene and observe the results. They were successful in developing a procedure to knock out the GDF-8 (myostatin) gene in mice and the results were astounding (see the pictures below).

This experiment proved definitively that the myostatin gene limits how big an animal's muscles can become. This led to additional studies, including human studies. Researchers have shown that the HIV virus attaches to the myostatin gene and is responsible for muscle wasting in AIDS patients. Myostatin is thought to be overexpressed in some forms of muscular dystrophy. It may also be resposible for muscle wasting due to aging and chronic disease.

The ultimate demonstration that myostatin regulates muscle size in humans is the work of a man named Victor Conte of BALCO laboratories. He has shown that champion bodybuilder Flex Wheeler actually possesses a mutation that has resulted in the deletion of his myostatin gene (much like that in Belgian Blue Cattle). This goes on to prove something else that has always been suspected...that champion bodybuilders possess some sort of genetic gift that allows them to become much more muscular than the average person. It seems that champion bodybuilders may owe much more to their genetics than they do to their training, supplement or drug use.

So What Does This Mean for You?

This means that you too have a myostatin gene. You may have a low, medium or high level of myostatin expression. The higher the level of your myostatin expression the less muscle mass you will build. Through millions of years of evolution you have arrived with a level of myostatin expression that is optimal for you. As you become stronger, you will produce a degree of muscle growth that allows you optimal mechanical and metabolic efficiency. It may not be the amount of muscle you had in mind for yourself, but for your body it will be the perfect amount. For the vast majority of women, there is no need to worry about muscles that are too large. For many men, you may not ever develop Mr. Universe muscles. But anyone can be certain of this...If you use proper exercise to stimulate maximal strength gains you will also develop the degree of muscle growth that is optimal for your own physiology. When this happens, you will also possess the degree of muscle that will be most attractive on your particular skeletal framework. How much myostatin do you have? There is only one way to find out.