title: Patterns of Age-Associated Degeneration Differ in Shoulder Muscles.
abstract: 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 (MRA) 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.
authors.affiliation: Department of Orthopaedics, Leiden University Medical CenterLeiden, Netherlands; Department of Molecular Epidemiology, Leiden University Medical CenterLeiden, Netherlands.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Raz
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Henseler
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Kolk
authors.affiliation: Department of Human Genetics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Riaz
authors.affiliation: Department of Orthopaedic Surgery, Medical Center Haaglanden Hague, Netherlands.
authors.forename: Peer
authors.initials: P
authors.lastname: van der Zwaal
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Jochem
authors.initials: J
authors.lastname: Nagels
authors.affiliation: Department of Orthopaedics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Rob G H H
authors.initials: RG
authors.lastname: Nelissen
authors.affiliation: Department of Human Genetics, Leiden University Medical Center Leiden, Netherlands.
authors.forename: Vered
authors.initials: V
authors.lastname: Raz
keywords: MRA; aging; fatty infiltration; fibrosis; muscle atrophy; rotator cuff tear; satellite cells; shoulder