Stephen Alway, PhD, has dedicated his career to unraveling the mysteries of sarcopenia, the age-related degeneration of muscle mass and strength. A professor in the Department of Physical Therapy and the Department of Physiology, and the director of the Center for Muscle, Metabolism, and Neuropathology at the University of Tennessee Health Science Center, his work has become particularly relevant as society faces the realities of an aging population.
Growing up on a dairy farm, Dr. Alway had a curiosity to explore the creation around him. This drove him at a young age to begin to understand skeletal muscle structure and function and why there was deterioration in the function of older people he met. “As a farmer, my dad was very active and still is, but some of his friends get up in the morning, they eat, and they go to the doctor, and they come home, and they eat, and that’s their existence,” he says, describing a reality familiar to anyone with aging parents. “It’s really a survival. It’s not a thriving.”
He hopes his research will change that.
His work, supported by the National Institutes of Health and various foundations, focuses on the cellular and molecular adaptations that occur in muscles as they age, especially concerning muscle loading, exercise, and periods of disuse. “My lab is interested in how muscles regenerate, and if there are ways to repair muscle more rapidly than just traditional exercise and waiting,” he says. This curiosity has led him to explore the role of muscle stem cells. “The stem cells along with mitochondria in this wonderful creation we call skeletal muscle are responsible for muscle regeneration. With aging or muscle disuse, they just don’t initiate repair the way they were designed to do.”
One of his current projects, funded by the United States Department of Defense, investigates the potential of mitochondria in muscle repair. Traditionally viewed as the cell’s powerhouse, mitochondria are now understood to play a far more complex role, including muscle growth. “If we go through bed rest or injury, those mitochondria get sick, they get leaky, and they actually can cause a lot of tissue destruction and damage,” Dr. Alway says. His team is exploring transplanting healthy mitochondria into damaged tissues, aiming to boost the function of existing muscle stem cells.
Preliminary results are promising, indicating improved muscle strength, size, and endurance, with reduced fibrosis. “We’re looking at different tissue sources and different subcomponents of mitochondria to see which ones become the most effective for the repair process. It’s early in the timeline of trying to understand the whole process, and we don’t know yet the mechanisms that are responsible for this.”
This research is vital not only for elderly people recovering from surgeries but also for individuals who have suffered major injuries, such as soldiers in war zones. “You’d like to think that they could come back to full recovery and do it quickly,” he says, underscoring the real-world impact of his work.
In addition to his focus on muscle regeneration, Dr. Alway is tackling the issue of cancer cachexia, a debilitating condition that results in severe muscle wasting in cancer patients. Chemotherapy, while crucial for treating cancer, can further deteriorate muscle health. “We’re trying to understand how we can modulate the muscle itself to create additional mitochondria without necessarily having to transplant them,” he says. His team is exploring genetic, pharmacological, and nutritional strategies to bolster mitochondrial function and mitigate muscle wasting. “We’ve got some genetic models in mice that we are able to manipulate and we’re also looking at how muscles repair under those conditions.”
Other studies his lab has designed investigate how oxidative stress, aging, nutrition, and exercise impact muscle recovery. The team is particularly interested in the interactions between activity and nutritional interventions such as resveratrol (an activator of Sirtuin 1), green tea (which is rich in catechins), genetic regulators, and other regulators of satellite cell-activated muscle repair.
Ultimately, Dr. Alway’s vision goes beyond the confines of the laboratory. He points out the relevance of the principles of Geroscience, the study of aging with the aim of extending not just lifespan, but health span. “Although we may not be able to extend life indefinitely, we can live a healthier life longer,” he says. By focusing on improving the quality of life, Dr. Alway hopes to empower individuals to lead independent, fulfilling lives well into their later years. “We’d like to thrive, not just survive. And I think that’s how we’re hoping to impact the communities around us.”