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).

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-

Cysteine*/metabolism ; Oxidation-Reduction* ; Aging*/physiology ; Aging*/metabolism; Humans ; Aged ; Male ; Female ; Physical Functional Performance ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/physiology ; Contractile Proteins/metabolism ; Muscle Proteins/metabolism ; Aged, 80 and over

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 (VO 2 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 VO 2 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.
(© 2024 Battelle Memorial Institute and The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Update of: medRxiv. 2023 Nov 08:2023.11.07.23298224. doi: 10.1101/2023.11.07.23298224. (PMID: 37986748)

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Keywords: cysteine oxidation; fitness; muscle; posttranslational modifications; power; redox

K848JZ4886 (Cysteine)
0 (Contractile Proteins)
0 (Muscle Proteins)

Date Created: 20240209 Date Completed: 20240611 Latest Revision: 20240708

20240709

PMC11166363

10.1111/acel.14094

38332629