Proteomics Analysis of Skeletal Muscle in Healthy Humans

Authors

• C Ubaida-Mohein
• A Lyashkov
• R Tharakan
• M Gonzalez-Friere
• MD Shardell
• R Moaddel
• C Chia
• L Ferrucci

Abstract

Introduction: Muscle degeneration is a substantial cause of weakness and frailty and in older persons, but the cause of such degeneration remains unknown and no previous study assessed the human skeletal muscle proteome over the course of aging. We have examined the proteome of human skeletal muscle utilizing a TMT-based protein quantification approach in very healthy persons dispersed over a wide age-range. Methods: Skeletal muscle biopsies were collected from 60 healthy human donors ranging in age from 22 to 87 years. Tandem Mass Tag (TMT) 6+ was used for relative protein quantification. Skeletal muscle proteins were extracted, trypsin digested, reduced and alkylated. MS/MS peaks from the samples were searched and analyzed. For final representation, spectra were normalized by median polish and median sweep, protein identifications were quantified, and annotated. Results: Relationships of protein levels with aging were examined by linear regression model. Several functional classes of proteins were found to be altered during aging, including contractile proteins, mitochondrial proteins, metabolism proteins, assembly complex proteins, innate immune proteins and proteins involved in gene expression. Proteins that maintain cellular physiology, biogenesis and cell cycle were also dysregulated with the course of aging. We found an age dependent decline of TCA cycle, respiratory chain, glycolysis and the electron transport pathway proteins. An age dependent increase in major spliceosome complex proteins was also evident. Conclusion: Our preliminary analysis shows that the skeletal muscle proteome undergoes substantial changes with healthy aging, indicating profound changes in energy metabolism and spliceosome complex.

Scientific Focus Area: Molecular Biology and Biochemistry

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