An NCI-designated Comprehensive Cancer Center
By Samuel LaBarge | March 7, 2012

Samuel LaBargeLower organisms such as planarians, axolotls and zebra fish can regenerate with great breadth; from entire half portions of a body, to whole limbs and hearts, respectively. As adult mammals, we are aware of our own limited capacity for regeneration. After a simple wound it can take more than a few days to heal and even longer for a scar to fade. In skeletal muscle, regeneration is important as a homeostatic response to damage and as a means to preserve function. This is especially important after an extensive period of exercise and conversely after an extensive period of sitting on the couch. The capacity of our skeletal muscle to regenerate following extensive damage or maintain homeostasis after extended periods of inactivity is extremely important. Loss of skeletal muscle function (regeneration and homeostasis) can severely decrease your quality of life. This is especially evident in elderly populations.

As intellectually curious scientists, when we want to study the function of a system we try to insult that system and then observe the outcomes. Skeletal muscle regeneration proceeds along a well defined pathway, and knowing skeletal muscle can regenerate following damage allows a scientist to study that function. We typically study regeneration in model organisms (see above). This is important because we must first understand what is happening, at a molecular level in organisms that can regenerate, before we can attempt to copy or improve those processes in our own species. Using tools such as metabolic, physical or chemical insults to elucidate underlying physiological mechanisms, we can observe the outcomes of skeletal muscle regeneration.

Two such insults used to study skeletal muscle function are hind-limb unloading (physical) and cardiotoxin injection (chemical). Hind-limb unloading is of particular interest because this type of perturbation can be used to mimic the effects of space travel on skeletal muscle. In model organisms, hind-limb unloading is achieved through the suspension of a muscle. Without the constant demand of use, skeletal muscle atrophies (unloaded skeletal muscle is analogous to low gravity). This insult is important because it allows a scientist to study factors involved in sarcopenia, a crucial component in aging muscle. On the other hand, cardiotoxin injection depolarizes the skeletal muscle membrane leading to rapid degeneration and ultimately regeneration of new skeletal muscle. This type of insult is useful because it forgoes the need to damage muscle with extended periods of exercise or unloading and allows a scientist simply to study how skeletal muscle regenerates.

These tools allow us to understand the mechanisms of skeletal muscle function and regeneration and ultimately will help us to further explain why mammals have generally lost the capacity for regeneration. This in turn will give us insight into improving the function of skeletal muscle in diseased and aging populations.