The Effect of Long-Term Physical Disability and Aging on Extracellular Matrix Biogenesis in Human Skeletal Muscle

Physical inactivity and aging cause significant impairments in the functionality and mechanical properties of skeletal muscles, as well as remodeling of the extracellular matrix (ECM). We aimed to study the effect of long-term inactivity and age on the biogenesis of ECM in skeletal muscle. For quantitative mass spectrometry-based proteomic analysis and RNA sequencing, biopsy samples were taken from m. vastus lateralis in 15 young healthy volunteers, 8 young and 37 elderly patients with long-term primary osteoarthritis of the knee/hip joint – which is a model for studying the effects of inactivity on muscles. We detected 1022 mRNAs and 101 ECM and associated proteins (matrisome). An increase in the expression of two dozen highly abundant matrisome proteins, specific to elderly and young patients (in relation to young healthy people), was detected; however, changes in the expression of mRNA encoding matrisome regulators (enzymatic regulators and secreted proteins) were similar. Comparison with previous proteomic and transcriptomic data showed that the changes in the matrisome that we described differed markedly from the changes caused by aerobic physical training in young healthy people, in particular, in the expression of the dominant ECM proteins and, especially, in the expression of mRNA of ECM enzymatic regulators and secreted proteins. Comparison of the changes in the expression profiles of these regulatory genes may be useful for identifying pharmacological targets for the prevention of adverse changes/activation of ECM biogenesis under various pathological conditions/physical training.