Stem cells support tissues by generating a supply of daughter somatic cells to replace losses. A broad body of evidence points to reduced muscle stem cell activity as a major contributing cause of age-related loss of muscle mass and strength. Other evidence suggests that this stem cell population remains capable; when old muscle stem cells are removed from the aged tissue environment for assessment, they appear to be as capable as young muscle stem cells. Researchers are now interested in establishing how an aged environment interacts with muscle stem cells to reduce their activity, with an eye to developing therapies to interfere in specific mechanisms as they are uncovered.
Frailty arising from loss of muscle function and mass is a significant health concern impacting quality of life and dramatically increasing health care costs as our population ages. Ameliorating frailty derived from reduced muscle function is thus a critical research priority to improve health span. Cell intrinsic defects in muscle stem cells (MuSC), or satellite cells, occur as skeletal muscle ages, reducing the capacity of MuSCs to maintain and repair skeletal muscle and are accompanied by cell nonautonomous changes.
Although rejuvenating stem cells in aged tissues or organs has potential to improve muscle aging phenotypes, we found that the extracellular environment in aged mice abrogates rejuvenated muscle stem cell potential. MuSCs from young mice were unable to grow on extracellular matrix derived from aged mice that contains elevated collagen protein levels, establishing a critical role for the environment in contributing to muscle phenotypes in aging. Combining an inducible FGF receptor 1 (FGFR1) to rescue MuSC intrinsic aging defects with a drug to reduce fibrosis partially rescued muscle mass loss in aged mice. We conclude that aging affects tissues, and particularly skeletal muscle tissue, via complex multifactorial processes requiring multifaceted interventions to improve aging phenotypes.
Link: https://doi.org/10.64898/2026.04.10.717808
View the full article at FightAging
