Aged Tendons Have Impaired Mechanosensitivity and Lower Thresholds for Injury under Dynamic Compression

model. Murine flexor tendon explants from young and aged animals were cultured in a biaxial bioreactor and subjected to different levels of dynamic compressive loading. We then observed changes in metabolic activity, matrix composition, matrix biosynthesis, matrix structure, and gene expression. Young tendons exposed to moderate levels of compression maintained homeostasis, whereas high compression induced a robust adaptive response characterized by increased glycosaminoglycan accumulation, elevated collagen content, and upregulation of remodeling-associated genes including collagen I, decorin, and MMP-9, as well as inflammatory and apoptotic markers. In contrast, aged tendons demonstrated a qualitatively different response, with transcriptional downregulation of key remodeling markers alongside elevated secretion of matrix-degrading enzymes and pro-inflammatory cytokines, indicative of a maladaptive mechanobiological response even at low compressive levels. These findings reveal that impaired mechanosensitivity and a lower threshold for injury may predispose chronically loaded tissues to degenerative pathology associated with excessive compressive loading.