Mechano-immune interactions in musculoskeletal aging: Mechanisms and translational perspectives

Mechano-immunology is an interdisciplinary field that examines how mechanical forces-including endogenous tissue stresses and exogenous stimuli-modulate immune cell function in the maintenance of homeostasis and the progression of disease. As the primary load-bearing framework of the body, the musculoskeletal system depends on coordinated mechanical loading to sustain immune balance and tissue repair. With aging, reduced physical activity, progressive matrix stiffening, and impaired mechanosensing in immune-cells converge to disrupt this mechano-immune axis, undermining immune clearance, inflammatory regulation, and regenerative capacity within musculoskeletal tissues. These alterations collectively contribute to the onset and progression of osteoarthritis, osteoporosis, and other degenerative musculoskeletal disorders. This review summarizes current advances in understanding the mechanisms of mechano-immunology within the musculoskeletal system under physiological conditions and delineates its involvement in the initiation and progression of degenerative diseases. Emerging strategies, including exercise-based interventions, controlled mechanical stimulation, and biomaterial engineering approaches targeting mechano-immune pathways, are also discussed as potential means to restore musculoskeletal homeostasis during aging.