When a hurricane tears through a house, the first step in recovery is to remove the wreckage before any rebuilding can begin. A similar process occurs within our muscles after they’ve been damaged—debris must be cleared to allow healing to take place. Now, researchers from Aarhus University and the Steno Diabetes Centre Aarhus have identified the key players responsible for managing this complex repair process. In a recent study published in Nature Communications, the team reveals a previously unrecognised form of cellular communication that orchestrates muscle healing and could have profound implications for treating muscle degeneration, particularly in elderly individuals.
The central discovery revolves around specialised cells known as fibro-adipogenic progenitors, or FAPs. These cells reside within muscle tissue and have long been recognised for their supporting role in muscle regeneration. However, the new research reveals that they do far more than assist—they act as coordinators, directing the immune system’s response to injury. Associate Professor Jean Farup, who led the study, likens their function to that of a foreman guiding a team of builders. By communicating with immune cells, particularly macrophages, FAPs facilitate the clearance of damaged tissue and ensure the necessary cellular machinery is in place for effective repair.
Macrophages serve as the body’s “clean-up crew,” removing cellular debris and stimulating regeneration. But what surprised the research team was the extent of the interaction between FAPs and these immune cells. Farup explains that FAPs actively influence the macrophages, enhancing their performance through targeted signalling. One of the most unexpected findings was that FAPs themselves produce a critical molecule known as complement C3. Until now, scientists believed C3 was produced exclusively in the liver and circulated through the bloodstream. This study, however, shows that C3 is also synthesised locally within muscle tissue, and that this local production is vital for regulating the inflammatory response required for healing.
This insight challenges long-standing assumptions about the source and role of inflammatory signalling during muscle repair. The presence of locally produced C3 suggests a far more refined and spatially controlled healing process than previously understood. In practical terms, this could lead to the development of treatments that enhance or mimic the role of FAPs, especially in individuals whose muscle regeneration is impaired due to age or chronic illness. The ability to modulate local inflammation more precisely could be the key to preventing long-term muscle wasting and preserving strength and mobility in later life.
For the elderly and patients with chronic diseases like type 2 diabetes, cardiovascular disease, or cancer, this discovery offers a new therapeutic avenue. Muscle loss in these populations is often driven by chronic, unresolved inflammation that impairs the repair process and accelerates decline. By targeting the newly identified communication pathway between FAPs and immune cells, scientists may be able to dampen harmful inflammation while preserving the beneficial aspects needed for recovery. “We believe that our new understanding of the interaction between FAPs and the immune system can be important in managing these conditions,” says Farup.
Moving forward, the Aarhus research team plans to investigate how this cellular coordination behaves in disease states marked by persistent inflammation. Their goal is to determine whether therapies that modulate FAP function or mimic their communication with macrophages could halt or even reverse muscle loss in affected patients. As our understanding of muscle regeneration deepens, so too does the possibility of restoring health and resilience to those whose bodies have long struggled to recover. This discovery may mark the beginning of a new era in the treatment of muscle-wasting conditions.
More information: Jean Farup et al, Complementing muscle regeneration—fibro-adipogenic progenitor and macrophage-mediated repair of elderly human skeletal muscle, Nature Communications. DOI: 10.1038/s41467-025-60627-2
Journal information: Nature Communications Provided by Aarhus University
