Scientists discover how muscle stem cells “flip the switch” to rebuild damaged muscles

Scientists at the University of California, Irvine School of Pharmacy and Pharmaceutical Sciences have discovered how muscle stem cells “flip the switch” to rebuild damaged muscle – a discovery that could help address the muscle loss associated with aging, injury and widely used weight-loss drugs.

The study, published this week nature metabolismShows that muscle recovery isn’t just about protein or exercise. It depends on timing and how the muscle cells use fuel.

Researchers found that immediately after stress, muscle stem cells temporarily slow down energy production. Instead of burning glucose for energy, they turn it to protective repair processes to produce antioxidants that reduce Swelling. Once repair is complete, energy production increases again and new muscle fibers form and strengthen.

Muscle metabolism isn’t just about promoting growth; It’s about strategic recovery. We found that muscle stem cells actively change how they use nutrients to first protect themselves, then rebuild. That metabolic time is important.”

Lauren Albrecht, UC Irvine assistant professor of pharmaceutical sciences and corresponding author of the study

At the center of the discovery is an enzyme called PFKM, which helps control how cells process glucose. The team determined that cells deliberately reduce PFKM levels during initial repair, leading to a temporary metabolic halt. When PFKM returns, muscle building begins.

Importantly, scientists showed that this process can be influenced. By supplying specific metabolic building blocks – nutrients that cells naturally produce later in recovery – they accelerated the transition from repair mode to growth mode in laboratory models.

The findings come as physicians and researchers grapple with the broader challenge of age-related muscle decline, along with increasing reports of lean muscle loss in patients using GLP-1-based weight loss drugs.

“With the rapid advancement of GLP-1 therapy and aging populations, preserving muscle mass has become a major health priority,” Albrecht said. “Our work identifies a metabolic checkpoint that may one day be targeted to help people recover muscle more effectively.”

The work combined advanced imaging, metabolic analysis and human muscle data to reveal how quickly these fuel transformations occur, sometimes within minutes. Researchers from UCLA and Yale University also participated.

The study was supported by the National Institute of General Medical Sciences, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Cancer Institute, and the Alfred P. Sloan Foundation.