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

European Journal of Applied Physiology volume 117, pages 1463–1472 (2017)Cite this article

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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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Abbreviations

ActRIIB:

Activin type IIB receptor

ECM:

Extracellular matrix

MRFs:

Muscle regulatory factors

TGF-β:

Transforming growth factor beta

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Acknowledgements

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

  1. Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia

    Lewan Parker, Pazit Levinger & Itamar Levinger

  2. Molecular Nutrition Unit, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, Australia

    Marissa K. Caldow, Rani Watts & David Cameron-Smith

  3. Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Australia

    Marissa K. Caldow

  4. Centre for Exercise and Nutrition, The Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, VIC, Australia

    Rani Watts

  5. Liggins Institute, The University of Auckland, Auckland, New Zealand

    David Cameron-Smith

  6. Australian Institute for Musculoskeletal Science (AIMSS), Western Health, St Albans, Victoria, Australia

    Itamar Levinger

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  1. Lewan Parker
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  2. Marissa K. Caldow
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  4. Pazit Levinger
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Contributions

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.

Corresponding author

Correspondence to Itamar Levinger.

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There are no conflicts of interest to disclose.

Additional information

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). https://doi.org/10.1007/s00421-017-3639-4

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  • DOI: https://doi.org/10.1007/s00421-017-3639-4

Keywords

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