The Genetics of Muscle Fitness

There are three types of muscles: smooth, cardiac, and skeletal. Smooth muscles help move food and fluids through your body. Cardiac muscles pump blood through your heart. Skeletal muscles are the kind that attach to your bones. They allow you to run, dance, lift, turn, and, in general, move through your environment. Physical fitness involves resilience in all muscle types. For this essay, however, our focus will be on the more physically apparent skeletal muscles, which can account for up to 40 percent of your total mass.

Muscle tissue is energetically expensive to maintain. Even at rest, your skeletal muscles consume about 25 percent of your energy. Thus, it is not in your body’s interest to have more muscle mass than it needs. For this reason, our muscles adapt. If we exercise a lot, our muscles become bigger and stronger. Conversely, muscles wither away without exercise—a fully immobilized muscle loses about one third of its mass within weeks. From personal experience we know that muscles are responsive to use. But how is this accomplished? Why is it that when you exercise your muscles get stronger and when you don’t they get weaker? The answer is that exercise involves more than your muscles. When you exercise, you are also exercising your DNA.

DNA holds the information for how to build proteins. This includes all the proteins associated with the building your muscles, of which there are two kinds. First, there are the proteins that actually become part of your muscles. Second, there are “regulator” proteins that serve to direct the building of your muscles. These regulator proteins act like managers at a construction site in that they determine when the building should speed up or slow down. If DNA gets a signal that more muscle mass is needed, then it creates more regulator proteins that are designed to speed up muscle protein synthesis where needed. Likewise, if DNA gets a signal that muscle production needs to slow down, it creates more regulator proteins designed to inhibit muscle protein synthesis. So, you see, DNA is the master controller. It actually produces hundreds of different muscle regulator proteins and each one has a specific purpose.

Regulator proteins also play a role in how much energy is made available to muscles. An example is the GLUT regulator protein, which sits on the surface of muscle tissue. Its function is to pull glucose, an energy-rich sugar molecule, from the bloodstream and into the muscle. You always have some GLUT proteins to enable muscle movement. As you exercise, however, you stimulate your DNA to create more of these proteins. A single decent exercise routine causes a significant increase in GLUT proteins. What this means is that your muscles can now pull glucose more efficiently out of your bloodstream, even while you are at rest. If you were to eat a potato, your blood sugar level would not rise as much as it would have otherwise.

GLUT proteins generally degrade after 24 hours. With continued exercise, your DNA replenishes the GLUT proteins and eventually an optimal number of them are retained. If you were to stop exercising, their positive effects would naturally fade away within a day or two. With zero exercises over many years, your DNA becomes inefficient at producing GLUT proteins. The result is unusually high blood sugar levels and a disease called type II diabetes.

Most of the energy used by your cells comes from a high-energy molecule known as ATP. ATP is produced using energy that comes from the oxidation of food. This occurs in small cellular organelles called mitochondria. How efficient mitochondria are at producing ATP is a function of the number of regulator proteins they contain. So what produces these regulator proteins? Your DNA. What happens when you exercise? You stimulate your DNA to make more of these regulator proteins within mitochondria, hence, more ATP becomes available to your cells, including your muscle cells. It takes about a week for the number of these regulator proteins to double. After about a month of regular exercise you reach a plateau. In everyday language you would say you are “in shape.” What you really mean, however, is that your DNA is in shape because it is now producing an optimal number of regulatory proteins that produce an optimal amount of ATP so that you are fit to perform physically demanding tasks, like running a marathon. So what happens when you don’t exercise? ATP production is minimized and the energy of food is directed to the production of energy-storage tissues, such as fat. Why does the body produce fat? So that the precious energy it contains might be available for labor-intensive activities at a later date, perhaps, when food is not so abundant.

Our bodies are smart, but the rules of the game have recently changed. For many thousands of years we relied on our DNA-mediated performance mechanisms to allow us to hunt, gather, and grow food, to build shelters, and walk far distances. These are all very labor-intensive activities. It has only been within the last 100 years that such activities have become mechanized. We walk much less because we have cars. We gather our own food much less because we have grocery stores. The U.S. Center for Disease Control and Prevention has noted a growing increase in obesity that coincides with the rise in sedentary lifestyles. While obesity can be traced to the intake of food as well as the quality of that food, there is another half of the equation that often gets neglected, which is exercise. Our bodies are designed to be physically active. Harm comes to us when we neglect this calling.

MUSCLE DOPING 
Our knowledge of DNA is ever so recent, but we are already well on our way to learning how to control and tinker with its mechanisms. The IGF-I regulator protein speeds up muscle building processes. To build bigger and stronger muscle tissue, why don’t we simply inject IGF-I into our muscles? This doesn’t work because the IGF-I dissipates within hours. What is needed is a continual source of IGF-I. Toward this end, researchers have successfully implanted the DNA that codes for IGF-I within the muscles of rats, who, without exercise, develop up to 30 percent more muscle mass. With exercise, the genetically “doped” muscles of these super rats become nearly twice as strong.

The insertion of DNA into a person to allow for the creation of certain proteins is known as gene therapy. The idea of gene therapy was dreamed up soon after the discovery of the structure of DNA in the 1950s. Although the idea is straightforward, it is only within the past decade, after years of intensive basic research, that success is starting to be realized. Muscle-enhancement gene therapy is poised to become one of the first gene therapies to be made available to the general population. Such therapy holds great promise for the treatment of muscular dystrophy as well as for the treatment of muscle weakness that comes with age. But it also raises a number of interesting questions. How safe is the procedure? Might such therapy lead to cancer? Are inherent risks worth the benefits? Will we be more or less likely to exercise after having our muscles doped with muscle-strengthening DNA? Should athletes be allowed to genetically dope their muscles for better performance? How about military personnel? The ethical issues surrounding genetic enhancement are many and complex.

Concept Check
What do seven days without exercise make?

Check Your Answer
Seven days without exercise makes one weak. Got it? Good. Now get to it.

In the Spotlight Discussion Questions

1. Should athletes be allowed to genetically dope their muscles for better performance? If so, should there be two sets of Olympics? One for the doped and another for the non-doped? Many Olympians may already benefit from natural mutations that enhance their performance. Why not level the playing field by making such enhancements available to all atheletes?

2. A new line of drugs known as nootropics are being developed to help us learn good (sic). Consider the social implications. What parallels might there be between sports-enhancing drugs and these intelligence-enhancing drugs? If these drugs are found to be safe, should they be available only by prescription? If they are found to be unsafe, should they be banned or should they be controlled like alcohol and tobacco?

3. Gene therapy is not passed along to offspring because it does not affect our reproductive cells. For an individual, however, a single dose may last a lifetime. So, what restrictions should be placed on muscle enhancement gene doping? Should it be allowed only for the treatment of medical conditions? Should it be made available only to people over the age of 21?

4. Might gene therapy ever become as routine as vaccinations? By when? What might be some social or political hurdles to an acceptance of such therapies?

5. How much would you be willing to pay for effective muscle enhancement gene therapy?

6. Muscle-enhancement gene therapy also interferes with fat deposition. How might the food industry respond to a population of consumers who could eat all they want and remain trim without much exercise?

Copyright, 2016, John Suchocki