Early Signs Of Extra Cellular Matrix Remodeling After Immobilization In Old And Young Human Individuals

Abstract

Skeletal musle disuse has been shown to induce muscle atrophy rapidly in both young and old human individuals (1) as well as extracellular matrix (ECM) remodeling in young individuals (2). However, little is known about the effect of immobilization on ECM remodeling in older individuals. PURPOSE: To study the effect of aging on transcriptional regulatory signaling pathways involved in ECM remodeling with short-term immobilization. METHODS: Myofiber atrophy was induced by application of a knee-brace for a total period of 4 days in young (Y∼20 yrs, n=11) and aged (O∼70 yrs, n=11) individuals. Muscle biopsies of the vastus lateralis (VL) muscle were collected 1 week prior to immobilization and after 24h, 48h and 96h of immobilization. Expression levels of Col1A1, Col3A1, MMP2 and MMP9 mRNAs were determined using real-time RT-PCR and normalized to the Ribosomal Protein Large P0 (RPLP0) mRNA. RESULTS: In both age groups an increase in expression levels of Col1A1, Col3A1, MMP2 and MMP9 mRNA was observed after 24h. In contrast, expression levels of Col1A1 and Col3A1 mRNA were up regulated at 48h and 96h primarily in old individuals and an overall effect of age was observed. The expression level of MMP2 mRNA was not changed from pre at 48h and 96h. The expression level of MMP9 mRNA was up regulated in both age groups at all three time points. CONCLUSIONS: The present data demonstrates early (post 24h) signs of ECM remodeling in both young and old individuals. Moreover, the results point toward an age specific regulation of ECM in response to muscle disuse, with an up regulation of collagen I and III in old only after 48h and 96h of immobilisation. REFERENCES 1) Suetta C et al. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy. PLoS One. 2012;7(12) 2) Reich KA et al. Forty-eight hours of unloading and 24 h of reloading lead to changes in global gene expression patterns related to ubiquination and oxidative stress in humans. J Appl Physiol 109: 1404-1415, 2010.