As people age, their muscles often weaken, leading to increased risks in daily activities such as getting out of bed. Sarcopenia, or low muscle mass in older adults, is a significant health concern that increases the likelihood of hospitalization and susceptibility to falls and fractures.
Alessandra Sacco, PhD, dean of the Sanford Burnham Prebys Medical Discovery Institute Graduate School of Biomedical Sciences and professor in the Center for Cardiovascular and Muscular Diseases, stated: "The progressive loss of skeletal muscle mass and function are indicators of poor survival in patients." She added, "It is absolutely crucial that we are able to develop strategies to maintain muscle as we age."
On December 5, 2025, Sacco and her research team published findings in Communications Biology identifying a protein called tenascin-C (TnC) as important for maintaining functional muscle stem cells needed for muscle regeneration. The study showed that TnC levels decrease with age, which contributes to a decline in both muscle stem cells and the ability to repair muscle tissue.
Previous research by the team indicated that pathways active during embryonic development are reused during tissue repair. Sacco explained: "TnC normally is not really expressed in healthy adult muscle, but it goes up rapidly after an injury to reactivate the programs needed for regeneration and repair." She continued: "We wanted to understand how TnC influenced stem cells that are primarily responsible for muscle regeneration, and how this relationship was affected by aging."
In experiments using mice lacking TnC, researchers observed fewer muscle stem cells compared to normal mice. Cecchini noted: "The stem cells also were less able to make new stem cells and maintain an adequate population, and this resulted in defects in their ability to repair injured muscle."
Further investigation revealed that support cells known as fibroadipogenic progenitors secrete TnC. Sacco said: "We found that support cells called fibroadipogenic progenitors were secreting TnC, which made sense given the known role of these during muscle regeneration." The team also discovered that TnC interacts with muscle stem cells through a receptor called Annexin A2.
"Revealing these players is a bit like identifying musicians in an orchestra," Cecchini said. "Just as each instrument contributes to the overall composition, now we can learn more about how different signals from each cell type are coordinated to repair muscle."
The study found that aged mice had lower levels of TnC and reduced ability for their muscle stem cells to migrate toward injury sites. Treating aged mouse muscle stem cells with TnC improved this defect. Sacco summarized: "We've shown that mice lacking TnC exhibit a premature aging phenotype, and that restoring TnC may be a therapeutic strategy for age-related muscle loss."
However, delivering TnC therapeutically remains challenging due to its size; further research will focus on finding effective delivery methods. Sacco's team continues work on potential solutions.
"Our overall goal is to contribute to a greater quality of life as we age," Cecchini said.
Sacco concluded: "Advances in science, medicine and public health have considerably extended the average lifespan. Now we need to make the same improvements to the healthspan, beginning by addressing frailty, falls and fractures."
