Lewan Parker1, Marissa K Caldow2,3, Rani Watts2,4, Pazit Levinger1, David Cameron-Smith2,5, Itamar Levinger6,7. 1. Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia. 2. Molecular Nutrition Unit, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, Australia. 3. Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Australia. 4. Centre for Exercise and Nutrition, The Mary MacKillop Institute for Health Research, Australian Catholic University, Fitzroy, VIC, Australia. 5. Liggins Institute, The University of Auckland, Auckland, New Zealand. 6. Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, PO Box 14428, Melbourne, VIC, 8001, Australia. itamar.levinger@vu.edu.au. 7. Australian Institute for Musculoskeletal Science (AIMSS), Western Health, St Albans, Victoria, Australia. itamar.levinger@vu.edu.au.
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.
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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