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

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Abstract

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.

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About the authors

N. S. Kurochkina

Institute of Biomedical Problems of the RAS

Author for correspondence.
Email: nadia_sk@mail.ru
Russian Federation, Moscow

E. M. Lednev

Institute of Biomedical Problems of the RAS

Email: nadia_sk@mail.ru
Russian Federation, Moscow

M. A. Orlova

Institute of Biomedical Problems of the RAS

Email: nadia_sk@mail.ru
Russian Federation, Moscow

M. A. Vigovskiy

Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Medical Research and Educational Center

Russian Federation, Moscow

V. G. Zgoda

Institute of Biomedical Chemistry

Email: nadia_sk@mail.ru
Russian Federation, Moscow

N. E. Vavilov

Institute of Biomedical Chemistry

Email: nadia_sk@mail.ru
Russian Federation, Moscow

T. F. Vepkhvadze

Institute of Biomedical Problems of the RAS

Email: nadia_sk@mail.ru
Russian Federation, Moscow

P. A. Makhnovskii

Institute of Biomedical Problems of the RAS

Email: nadia_sk@mail.ru
Russian Federation, Moscow

O. A. Grigorieva

Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Medical Research and Educational Center

Russian Federation, Moscow

Y. R. Boroday

Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Medical Research and Educational Center

Russian Federation, Moscow

V. V. Philippov

Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Medical Research and Educational Center

Russian Federation, Moscow

M. Yu. Vyssokikh

Institute of Biomedical Problems of the RAS; Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Belozersky Institute of Physico-Chemical Biology

Russian Federation, Moscow; Moscow

A. Yu. Efimenko

Lomonosov Moscow State University

Email: nadia_sk@mail.ru

Medical Research and Educational Center

Russian Federation, Moscow

D. V. Popov

Institute of Biomedical Problems of the RAS

Email: nadia_sk@mail.ru
Russian Federation, Moscow

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2. Fig. 1. Chronic physical inactivity in older (OP vs YH) and younger adults (YP vs YH) results in partially overlapping changes in mRNA (padj < 0.01) and protein (padj < 0.05) expression of the matrisome in the vastus lateralis muscle. The amounts of common and unique mRNAs (A and B) and proteins (B) are shown in the overlapping and non-overlapping areas of the diagrams. Potential protein-protein interactions are shown as lines; line thickness is proportional to the relevance of the interaction.

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3. Fig. 2. Changes in the mRNA expression profile of secreted factors (A) and enzymatic regulators of the ECM (B) in the vastus lateralis muscle during chronic physical inactivity in older (OP vs YH) and younger adults (YP vs YH) and after 2 months of aerobic training. Only significant changes (padj < 0.01) are presented as log2.

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4. Fig. 3. Changes in expression of genes encoding mRNA (padj < 0.01) and proteins (padj < 0.05) of the matrisome in m. vastus lateralis after 2 months of aerobic training are significantly different from changes induced by chronic physical inactivity in elderly (OP vs YH) and young adults (YP vs YH). The number of common and unique mRNAs (A and B) and proteins (B) is shown in overlapping and non-overlapping areas of the diagrams. Potential protein-protein interactions are shown as lines; line thickness is proportional to the relevance of the interaction.

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