The following is an adapted excerpt from the forthcoming book “Chasing Captain America: How Advances in Science, Engineering and Biotechnology Will Produce a Superhuman.
Citius, altius, fortius. Faster, higher, stronger. The modern Olympic motto was proposed by Pierre de Coubertin when the International Olympic Committee was formed way back in 1894. It’s meant to capture the essence of competition in sport but is also a signal for many to try and exceed human biological limits by using external enhancements in the form of “doping.” A very well-known example of doping in sport is the use of androgenic steroids. What people outside of strength-training circles don’t necessarily know, however, is that substances like steroids can still have an effect after athletes stop using them.
Even without steroids, someone who has trained extensively and then stopped, reacquires muscle mass and strength more rapidly than someone who hadn’t trained at all. This was thought to be due to rapid changes in the nervous system affecting the coordination and activation of the muscles, which might in turn related to what scientists call epigenetics.”
There was much excitement when the human genome was first sequenced a decade and a half ago, but the latest hot topic—and one with significant impact for doping, suspension, and possible return to play—is the epigenome. The epigenome determines which genes actually get activated and expressed by what kind of cells, and when. If the genome contains the essence of your genetic potential, epigenetics is the way your potential—all your ability for faster, higher, stronger—is brought forward and used. The genome is like a dictionary full of words, most of which aren’t all used at once—and some of which are never used at all. Epigenetics is the process of pulling those words out and usefully applying them in sentences for the conversations you need to have. Epigenetics essentially bridges the gap between nature and nurture.
More specifically, it describes how gene expression is regulated and what genes are expressed in an organism. This does not change the actual nucleotide sequences—the building blocks—in the genes. The epigenetic changes that happen to you in the course of your life affect the next generation of cells that you produce.
While every cell in your body carries your genome, your epigenome has a number of flavors, depending upon the cell and tissue type. The key things about epigenetics are that it affects gene expression, changes during development (when stem cells are differentiating into the cells they are going to become), and changes in disease states.
Cancer, of all diseases, has been the one linked most clearly with epigenetic changes. For example, a gene that when activated produces lung cancer might only be expressed and activated when an environmental cue is present, like cigarette smoke. But biology isn’t typically that simple: linking diseases directly to DNA changes is difficult. This is largely because changes that yield disorders often occur outside the parts of the DNA that code for proteins and that we understand better.
This is where biologist Ingrid Egner and her colleagues in Norway enter the story. They were interested in the effect of training on muscle growth. Unlike most other cell types, muscle fibers have multiple nuclei. During strength training, muscle mass increases, and the number of nuclei in each cell also goes up. This team wanted to know if this “cellular memory mechanism” could be influenced by steroids. They gave mice a testosterone derivative for 14 days, which produced about a 66 percent increase in nuclei and a 77 percent increase in the size of the muscle fibers. Three weeks after withdrawing testosterone, the size of the muscle fibers had reverted to the level found in animals that had never trained or been given drugs.
This part of the experiment was to cause a change in the “memory” within the nuclei of the muscle fibers. While the size of the fibers fluctuated, the number of nuclei remained elevated for three months after the testosterone was withdrawn. Did this mean that the muscle fibers would respond differently to training? That is, would they respond like “normal” or enhanced muscle because of the larger number of nuclei?
In the next part of the experiment, two groups of animals (the ones who were previously exposed to the testosterone derivative and the “control” animals that weren’t) were strength-trained for six days. Control mice failed to show any appreciable increase in muscle fiber size after this short period, while, in contrast, the testosterone-exposed mice showed a 31 percent increase.
Previously untrained muscle fibers recruit nuclei from activated satellite (stem) cells before growing larger. The nuclei are the command centers driving the muscle cells to produce more protein to get larger and stronger, and it seems that this greater number of nuclei is retained and protected over time. Muscle fibers with this higher number of nuclei then grow faster when given an exercise stress like strength training. This “memory” of prior strength apparently remains stable for up to 15 years and may be permanent.
The relevance for doping in sport is that even a brief period of anabolic steroid use may cause long-lasting performance enhancements that continue many years after use is discontinued. It is almost as if the “use it or lose it” adage has been changed to “depending upon what you used you might not really ever lose it.” We don’t’ know for sure how this may relate to other performance enhancing drugs. But if an athlete takes something to enhance her abilities very quickly and then stops, she may forever possess the enhanced ability to be retrained quickly.
In real life where there are no rules on competition, this is a great example of the plasticity of physiology. In sport it’s a great example of how citius, altius, fortius can be achieved in ways that circumvent the rules of competition.