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Age and sex differences in human skeletal muscle fibrosis markers and transforming growth factor-β signaling



The aim of the study was to determine whether higher fibrosis markers in skeletal muscle of older adults are accompanied by increased expression of components of the canonical TGF-β signal transduction pathway.


Fourteen healthy young (21–35 years; 9 males and 5 females) and seventeen older (55–75 years; 9 males and 8 females) participants underwent vastus lateralis biopsies to determine intramuscular mRNA and protein expression of fibrogenic markers and TGF-β signaling molecules related to TGF-β1 and myostatin.


Expression of mRNA encoding the pro-fibrotic factors; axin 2, collagen III, β-catenin and fibronectin, were all significantly higher (all p < 0.05) in the older participants (350, 170, 298, and 641%, respectively). Furthermore, axin 2 and β-catenin mRNA were significantly higher in older females than older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-β1 were higher in older adults compared to younger adults (all p < 0.05). There was, however, no difference in the total protein content of myostatin, myoD or myogenin (all p > 0.05), whereas Smad3 protein phosphorylation was 48% lower (p < 0.05) in muscle from older adults.


Increased abundance of mRNA of fibrotic markers was observed in muscle from older adults and was partly accompanied by altered abundance of pro-fibrotic ligands in a sex specific manner.

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Activin type IIB receptor


Extracellular matrix


Muscle regulatory factors


Transforming growth factor beta


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A/Prof. Levinger was supported by Future Leader Fellowship (ID 100040) from the National Heart Foundation of Australia. The authors wish to thank Dr. Andrew Garnham (Victoria University University) and Dr. Mitchell Anderson for performing the muscle biopsies.

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Authors and Affiliations



RW and MC carried out the experimental procedures; LP carried out the statistical analysis; DCS, IL and PL designed the study and collected the data. All authors assisted with drafting of the manuscript, critically reviewed the manuscript, and have read and approved the final version.

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Correspondence to Itamar Levinger.

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There are no conflicts of interest to disclose.

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Communicated by Fabio Fischetti.

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Parker, L., Caldow, M.K., Watts, R. et al. Age and sex differences in human skeletal muscle fibrosis markers and transforming growth factor-β signaling. Eur J Appl Physiol 117, 1463–1472 (2017).

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  • Aging
  • Myostatin
  • TGF-β
  • Fibrosis
  • Skeletal muscle