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

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-ß 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-ß signaling molecules related to TGF-ß1 and myostatin. RESULTS: Expression of mRNA encoding the pro-fibrotic factors; axin 2, collagen III, ß-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 ß-catenin mRNA were significantly higher in older females than older males (p < 0.05). Gene expression of ActRIIB, myostatin, and TGF-ß1 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.