If you coach, train, or treat athletes and patients, you’re aware that skeletal muscle adapts to the balance between building up (protein synthesis) and breaking down (protein breakdown). We’ve gotten remarkably good at measuring the “building up” side through stable isotope tracer methods, with newer methods enabling participants to orally consume them. The “breaking down” side has been a much harder nut to crack.
Measuring true muscle protein breakdown requires arterial and venous blood draws, blood flow measurements, and isotope infusions. Not only are these methods technically demanding and expensive, but they’re simply not feasible for most labs, let alone field or clinical settings.
That gap matters. Whether we’re trying to understand how muscle recovers from a hard training bout, why a limb withers after two weeks in a cast or boot, or how disease-related muscle wasting progresses, we need a marker of protein breakdown that’s practical to measure. My colleagues and I think we may have found a good candidate hiding in plain sight: myosin heavy chain (MyHC), the single most abundant protein in skeletal muscle, making up roughly 40% of the total muscle protein pool.
What we found
Using simple, low-cost western blotting, we discovered that intact MyHC protein forms smaller fragments (i.e., MyHC fragmentation) under several physiologically relevant conditions including:
1. After a single bout of resistance exercise, well-trained men showed a roughly 200% increase in MyHC fragmentation just 3 hours post-exercise, which then rapidly disappeared by 6 hours. The fast-twitch (type IIa) fibers fragmented considerably more than slow-twitch (type I) fibers.
2. In previously untrained adults, a first-time leg extension bout produced a similar fragmentation response 24 hours later — but after 10 weeks of training, that same bout produced a smaller response, suggesting the muscle had adapted after 10 weeks of habitual training and was experiencing less disruption.
3. Two weeks of leg immobilization roughly doubled MyHC fragmentation alongside ~8% muscle atrophy.
A 60-minute cycling bout, by contrast, produced no fragmentation at all, hinting that mechanical loading, not aerobic metabolic stress, is the trigger. In follow-up cell culture work, blocking calpain proteases (calcium-activated enzymes known to target structural muscle proteins) largely prevented the fragmentation, pointing to calpains as a likely mechanistic driver.
Michael Roberts, PhD, is a professor and director of the Nutrabolt Applied and Molecualr Physiology Laboratory in the School of Kinesiology at Auburn University. His research examines how exercise and nutritional supplements affect physiological outcomes in younger and older adults.
Emily Howard, PhD, is a nutrition physiologist at the US Army Research Institute of Environmental Medicine (USARIEM) where her research focuses on developing practical dietary interventions to optimize Warfighter health and performance during various environmental, operational, and clinical stressors. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the US Army, Department of War, or the US government.
