Exercise-Activated Mesenchymal Stem Cells: A Translational Strategy for Age-Related Sarcopenia Management

Age-related Sarcopenia is a progressive, age-related disorder characterized by the loss of muscle strength, mass, and function, which is associated with an increased risk of falls and mortality and reduced quality of life, particularly in older adults. The pathophysiology of sarcopenia is complex, primarily driven by an imbalance between anabolic and catabolic muscle homeostasis. Effective interventions of sarcopenia is crucial to reverse or delay the progression of muscle disorder. Cell-based therapy is emerging as an innovative approach for sarcopenia. Owing to their multipotent differentiation capacity, self-renewal ability, and immunomodulatory effects, mesenchymal stem cells (MSCs) offer a promising therapeutic avenue for sarcopenia through mechanisms such as tissue regeneration, paracrine signaling, and immune regulation. However, despite their potential, MSC-based therapies face limitations, including low engraftment efficiency and poor post-transplant cell survival. Emerging evidence suggests that combining MSC transplantation with exercise intervention may enhance therapeutic efficacy. In this review, we aimed to summarize the synergistic mechanisms underlying MSC-exercise interactions, with a focus on how exercise modulates MSC migration, differentiation, and muscle regenerative capacity. By addressing the limitations of standalone MSC therapy, this combinatorial strategy may pave the way for more effective age-related sarcopenia management. Finally, we highlight future research directions, underscoring the need for optimized exercise regimens, refined MSC delivery protocols, and translational studies to facilitate the clinical application of this integrated approach.