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

Physical inactivity and aging cause significant impairment of skeletal muscle functionality and mechanical properties, as well as remodeling of the extracellular matrix (ECM). The purpose of this work was to study the effect of chronic decrease in physical activity and age on the biogenesis of ECM in skeletal muscle. Biopsy samples from m. vastus lateralis were taken for quantitative mass spectrometry-based proteomic analysis and RNA sequencing in 15 young healthy volunteers and 8 young and 37 elderly patients with long-term primary osteoarthritis of the knee/hip joint as a model to study the effects of chronic muscle motor decline. In total, 1022 mRNAs and 101 ECM proteins and ECM-associated proteins (matrisome) were detected. An increase in the expression of two dozen highly abundant matrisome proteins specific to elderly and young patients (relative to young healthy subjects) was identified; however, changes in the expression of mRNAs encoding matrisome regulators (enzymatic regulators and secreted proteins) were similar. Comparison with previous proteomic and transcriptomic data showed that the described matrisome changes were markedly different from those induced by aerobic physical training in young healthy individuals, in particular in the expression of dominant ECM proteins and, especially, in the expression of mRNAs of ECM enzymatic regulators and secreted proteins. Matching the expression profiles of these regulatory genes may be useful for finding pharmacological targets for preventing adverse changes/activation of ECM biogenesis in various pathological conditions/physical training.