Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography in subjects without (N=294) and with (N=109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging-resilient muscle.

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radiological muscletendon units deltoid shoulder extracellular matrix muscles ageassociated fatty infiltration heavy fibrosis normalized muscle csa cross sectional area csa arthrography hallmarks of muscle aging histological rc muscle pathology satellite cells magnetic resonance imaging rotator cuff

Yotam eRaz,Jan Ferdinand eHenseler,Arjen eKolk,Muhammad eRiaz,Peer evan der Zwaal,Jochem eNagels,Rob G.H.H. Nelissen,Vered eRaz,.Patterns of age-associated degeneration differ in shoulder muscles. 7 (),.

Yotam eRaz,Jan Ferdinand eHenseler,Arjen eKolk,Muhammad eRiaz,Peer evan der Zwaal,Jochem eNagels,Rob G.H.H. Nelissen,Vered eRaz,"Patterns of age-associated degeneration differ in shoulder muscles" 7

Yotam eRaz,Jan Ferdinand eHenseler,Arjen eKolk,Muhammad eRiaz,Peer evan der Zwaal,Jochem eNagels,Rob G.H.H. Nelissen,Vered eRaz,"Patterns of age-associated degeneration differ in shoulder muscles"