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 8 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 impair muscle power and strength, walking speed, and cardiopulmonary fitness with aging.