Targeting the Skeletal Muscle Microenvironment: A Novel Therapeutic Strategy for Skeletal Muscle Aging

Sarcopenia, a hallmark of skeletal muscle aging, is a significant public health concern that substantially compromises the quality of life in the elderly. While conventional research has predominantly focused on intrinsic pathological alterations within muscle fibers, it has often overlooked the diverse cell–cell and interorgan communications mediated by nonmuscle cells in the skeletal muscle microenvironment. This microenvironment, comprising the extracellular matrix, multiple cellular components, secreted factors, and metabolites, plays a crucial role in regulating muscle homeostasis and regeneration, serving as a key driver of skeletal muscle aging. As the microenvironment undergoes profound remodeling with advancing age, this review systematically examines novel intervention strategies targeting it. By aiming to achieve coordinated multipathway remodeling of this niche, these approaches offer a fresh theoretical foundation and novel clinical avenues for delaying or reversing sarcopenia. Future research should prioritize elucidating these microenvironmental regulatory mechanisms, refining personalized intervention protocols, and rigorously validating translational applications.