Murine Supraspinatus Tendons Demonstrate Aging‐Related Changes in Multiscale Mechanics, Structure, and Gene Expression

Rotator cuff disorders are common in the aging population, often leading to pain, disability, and reduced quality of life. Age-associated changes can occur disproportionately in regions of high mechanical stress, such as the insertion site of the supraspinatus tendon, leading to increased injury rates and tendinopathies. We previously demonstrated site-specific differences in structure, function, and gene expression between the insertion and midsubstance regions of supraspinatus tendons in mature, Day 150 mice. However, a comprehensive study examining the role of aging on site-specific supraspinatus tendon multiscale structure, function, and gene expression is needed. Therefore, our objective was to elucidate the role of aging on supraspinatus tendon multiscale structure, function, and gene expression. Whole-tissue and regional mechanics, as well as regional fibril response to load, cellularity and cell shape, collagen fibril morphology, and gene expression were evaluated in supraspinatus tendons of Day 300 and Day 570 mice. Aging resulted in decreased stiffness, dynamic modulus, and decreased midsubstance modulus. Collagen fibril morphology analysis revealed a more noticeable shift toward smaller fibril diameters with aging in the midsubstance region. Histological evaluation demonstrated reduced cellularity and a transition to more elongated cell morphology in aged tendons. Gene expression profiling highlighted upregulation of pro-inflammatory and catabolic markers and downregulation of major collagens in Day 570 tendons relative to Day 300 tendons. Understanding the effects of aging on tendon structure, function and gene expression provides critical insights into the mechanisms underlying aging-related injury and tendinopathy.