• Aging transforms skeletal muscle ECM into a fibrotic barrier through collagen overdeposition, advanced glycation end-product cross-linking, and impaired signaling, creating a vicious cycle of component imbalance, physical stiffening, and functional decline.
• The pathological ECM remodeling is a critical driver of muscle aging, not merely a consequence, and represents a key therapeutic target.
• A three-tier intervention framework is proposed: restoring ECM homeostasis via exercise, clearing senescent cells to remove upstream drivers, and using tissue engineering for functional reconstruction.
• The 'pathological cycle-layered intervention' framework provides a foundation for developing combination therapies and personalized precision medicine for sarcopenia.