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)

Abstract

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.

Autophagy gene expression in skeletal muscle of older individuals is associated with physical performance, muscle volume and mitochondrial function in the study of muscle, mobility and aging (SOMMA)

“…This finding is congruent with reports that higher levels of circulating inflammatory mediators are associated with poor mobility in older adults (Penninx et al., 2004 ). While we have not probed markers of inflammation in this SOMMA dataset, we note that a separate analysis supports the concept that older adults with higher fitness/respiration/walking speed also have lower oxidative stress (Day et al., 2024 ; Tranah et al., 2023 ).…”

The cellular bases of mobility from the Study of Muscle, Mobility and Aging (SOMMA)

“…Day et al (2024) uses mass spectrometry-based redox proteomics in a sample of SOMMA F I G U R E 1 Using assays of samples of skeletal muscle from the vastus lateralis, studies from SOMMA show that mitochondrial generation of ATP, oxidative damage, reduced antioxidant defences (e.g. SOD2), autophagy, and denervation play important roles in mobility folder adults.…”

“…Day et al. ( 2024 ) uses mass spectrometry‐based redox proteomics in a sample of SOMMA participants to find that oxidative modifications of proteins essential to myocellular function are associated with decreased performance in several measurements of mobility. In a complementary analysis, Tranah et al.…”