Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Molecular signatures of age-associated chronic degeneration of shoulder muscles

Yotam Raz _, Jan Ferdinand Henseler, Arjen Kolk, Zuotian Tatum, Niels Kuipers Groosjohan, Nisha E. Verwey, Wibowo Arindrarto, Szymon M. Kielbasa, Jochem Nagels, Peter A. C. ’t Hoen, Rob G. H. H. Nelissen and Vered Raz

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Oncotarget. 2016; 7:8513-8523. https://doi.org/10.18632/oncotarget.7382

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Abstract

Yotam Raz1,2,3,*, Jan Ferdinand Henseler1,*, Arjen Kolk1, Zuotian Tatum2, Niels Kuipers Groosjohan2, Nisha E. Verwey2, Wibowo Arindrarto3, Szymon M. Kielbasa3, Jochem Nagels1, Peter A. C. ’t Hoen2, Rob G. H. H. Nelissen1 and Vered Raz2

1 Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands

2 Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

3 Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

* Equal first authorship

Correspondence to:

Vered Raz, email:

Keywords: shoulder disease, atrophy, fatty infiltration, muscle satellite cells, deep RNA-seq, Gerotarget

Received: January 08, 2016 Accepted: January 30, 2016 Published: February 14, 2016

Abstract

Chronic muscle diseases are highly prevalent in the elderly causing severe mobility limitations, pain and frailty. The intrinsic molecular mechanisms are poorly understood due to multifactorial causes, slow progression with age and variations between individuals. Understanding the underlying molecular mechanisms could lead to new treatment options which are currently limited. Shoulder complaints are highly common in the elderly, and therefore, muscles of the shoulder’s rotator cuff could be considered as a model for chronic age-associated muscle degeneration. Diseased shoulder muscles were characterized by muscle atrophy and fatty infiltration compared with unaffected shoulder muscles. We confirmed fatty infiltration using histochemical analysis. Additionally, fibrosis and loss of contractile myosin expression were found in diseased muscles. Most cellular features, including proliferation rate, apoptosis and cell senescence, remained unchanged and genome-wide molecular signatures were predominantly similar between diseased and intact muscles. However, we found down-regulation of a small subset of muscle function genes, and up-regulation of extracellular region genes. Myogenesis was defected in muscle cell culture from diseased muscles but was restored by elevating MyoD levels. We suggest that impaired muscle functionality in a specific environment of thickened extra-cellular matrix is crucial for the development of chronic age-associated muscle degeneration.


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