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Title: Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality
Authors: Schüler, Svenja C
Kirkpatrick, Joanna M
Schmidt, Manuel
Santinha, Deolinda 
Koch, Philipp
Di Sanzo, Simone
Cirri, Emilio
Hemberg, Martin
Ori, Alessandro
von Maltzahn, Julia
Keywords: aging; extracellular matrix; Integrin; muscle stem cell; niche; pERK; proteomics; satellite cell; skeletal muscle; Smoc2
Issue Date: 2021
Project: Federal Government of Germany and the State of Thuringia 
grant from the Deutsche Forschungsgemeinschaft to J.v.M. (MA-3975/2-1). 
Research Training Group ProMoAge (GRK 2155 
Else Kro¨ ner-Fresenius-Stiftung (award number 2019_A79) 
Deutsches Zentrum f€ur Herz-Kreislaufforschung (award number 81X2800193) 
Fritz Thyssen Foundation (award number 
Serial title, monograph or event: Cell Reports
Volume: 35
Issue: 10
Abstract: During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we use quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generate a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we reveal signaling by integrins, Lrp1, Egfr, and Cd44 as the major cell communication axes perturbed through aging. We investigate the effect of Smoc2, a secreted protein that accumulates with aging, primarily originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Integrin beta-1 (Itgb1)/mitogen-activated protein kinase (MAPK) signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.
ISSN: 22111247
DOI: 10.1016/j.celrep.2021.109223
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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