Journal Article

Signatures of cysteine oxidation on muscle structural and contractile proteins are associated with physical performance and muscle function in older adults: Study of Muscle, Mobility and Aging (SOMMA)

Attah, Isaac K., Cummings, Steven R., Trejo, Jesse B., Kritchevsky, Stephen B., Sagendorf, Tyler J., Gaffrey, Matthew J., Coen, Paul M., Kramer, Philip A., Goodpaster, Bret H., Qian, Wei‐Jun, Moore, Ronald J., Petyuk, Vladislav A., Mansfield, Tyler A., Newman, Anne B., Esser, Karyn A., Douglas, Collin M., Kelly, Shane S., Hepple, Russell T., Lui, Li‐Yung, Cawthon, Peggy M., Marcinek, David J., Day, Nicholas J.

2024

Overview

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community‐based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin‐1, myomesin‐2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin‐2, alpha‐actinin‐2, and skeletal muscle alpha‐actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha‐actinin‐3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging. In this study, we applied a novel redox proteomics approach to quantitatively profile the levels of oxidation on protein cysteines in muscle tissue of older adults to identify signatures that may distinguish among varying degrees of mobility. In general, increased levels of Cys oxidation on key sarcomeric proteins were found to be negatively associated with muscle function, physical performance, and fitness.

• Publisher: John Wiley & Sons, Inc,Anatomical Society - Wiley,John Wiley and Sons Inc
• Subject: Actin / Actinin / Aged / Aged, 80 and over / Aging / Aging - metabolism / Aging - physiology / BASIC BIOLOGICAL SCIENCES / Biopsy / Body weight / Contractile Proteins - metabolism / Cysteine / Cysteine - metabolism / cysteine oxidation / Enzymes / F-actin-binding proteins / Female / fitness / Humans / Hypotheses / Leg / Male / Mobility / Molecular modelling / muscle / Muscle contraction / Muscle function / Muscle Proteins - metabolism / Muscle, Skeletal - metabolism / Muscle, Skeletal - physiology / Older people / Oxidation / Oxidation-Reduction / Oxidative stress / Physical fitness / Physical Functional Performance / Physiology / post-translational modifications / posttranslational modifications / power / Proteins / Proteomics / redox / Regression analysis / Skeletal muscle / Special Section “Aging Cohorts: Resources for Translational Research” / Walking