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)

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

doi:10.1111/acel.14094

Title: 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)

Journal Article · Thu Feb 08 00:00:00 UTC 2024 · Aging Cell

DOI: https://doi.org/10.1111/acel.14094 · OSTI ID:2336567

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Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Biological Sciences Division
California Pacific Medical Center Research Institute, San Francisco, CA (United States)
University of Florida, Gainesville, FL (United States)
University of Pittsburgh, PA (United States)
Wake Forest University, Winston-Salem, NC (United States)
University of Washington, Seattle, WA (United States)
Translational Research Institute, AdventHealth, Orlando, FL (United States)
California Pacific Medical Center Research Institute, San Francisco, CA (United States); University of California, San Francisco, CA (United States)

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: Longevity Consortium; Molecular Transducers of Physical Activity Consortium; National Center for Advancing Translational Science; National Institute on Aging (NIA); USDOE Office of Science (SC); Wake Forest University

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2336567

Report Number(s):: PNNL-SA--192090

Journal Information:: Aging Cell, Journal Name: Aging Cell Journal Issue: 6 Vol. 23; ISSN 1474-9718

Publisher:: Anatomical Society - WileyCopyright Statement

Country of Publication:: United States

Language:: English

References (37)

limma: Linear Models for Microarray Data Smyth, G. K. Bioinformatics and Computational Biology Solutions Using R and Bioconductor https://doi.org/10.1007/0-387-29362-0_23	book	January 2005
Aberrations in Energetic Metabolism and Stress-Related Pathways Contribute to Pathophysiology in the Neb Conditional Knockout Mouse Model of Nemaline Myopathy Slick, Rebecca A.; Tinklenberg, Jennifer A.; Sutton, Jessica The American Journal of Pathology, Vol. 193, Issue 10 https://doi.org/10.1016/j.ajpath.2023.06.009	journal	October 2023
Effects of physical exercise therapy on mobility, physical functioning, physical activity and quality of life in community-dwelling older adults with impaired mobility, physical disability and/or multi-morbidity: A meta-analysis de Vries, N. M.; van Ravensberg, C. D.; Hobbelen, J. S. M. Ageing Research Reviews, Vol. 11, Issue 1 https://doi.org/10.1016/j.arr.2011.11.002	journal	January 2012
A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging Xiao, Haopeng; Jedrychowski, Mark P.; Schweppe, Devin K. Cell, Vol. 180, Issue 5 https://doi.org/10.1016/j.cell.2020.02.012	journal	March 2020
Hallmarks of aging: An expanding universe López-Otín, Carlos; Blasco, Maria A.; Partridge, Linda Cell, Vol. 186, Issue 2 https://doi.org/10.1016/j.cell.2022.11.001	journal	January 2023
The redox stress hypothesis of aging Sohal, Rajindar S.; Orr, William C. Free Radical Biology and Medicine, Vol. 52, Issue 3 https://doi.org/10.1016/j.freeradbiomed.2011.10.445	journal	February 2012
Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice Campbell, Matthew D.; Duan, Jicheng; Samuelson, Ashton T. Free Radical Biology and Medicine, Vol. 134 https://doi.org/10.1016/j.freeradbiomed.2018.12.031	journal	April 2019
Exercise stress leads to an acute loss of mitochondrial proteins and disruption of redox control in skeletal muscle of older subjects: An underlying decrease in resilience with aging? Pugh, Jamie N.; Stretton, Clare; McDonagh, Brian Free Radical Biology and Medicine, Vol. 177 https://doi.org/10.1016/j.freeradbiomed.2021.10.003	journal	December 2021
A deep redox proteome profiling workflow and its application to skeletal muscle of a Duchenne Muscular Dystrophy model Day, Nicholas J.; Zhang, Tong; Gaffrey, Matthew J. Free Radical Biology and Medicine, Vol. 193 https://doi.org/10.1016/j.freeradbiomed.2022.10.300	journal	November 2022
Three-Dimensional Structure of Vertebrate Muscle Z-Band: The Small-Square Lattice Z-Band in Rat Cardiac Muscle Burgoyne, Thomas; Morris, Edward P.; Luther, Pradeep K. Journal of Molecular Biology, Vol. 427, Issue 22 https://doi.org/10.1016/j.jmb.2015.08.018	journal	November 2015
Exercise-induced oxidative stress: Friend or foe? Powers, Scott K.; Deminice, Rafael; Ozdemir, Mustafa Journal of Sport and Health Science, Vol. 9, Issue 5 https://doi.org/10.1016/j.jshs.2020.04.001	journal	September 2020
Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle Kramer, Philip A.; Duan, Jicheng; Gaffrey, Matthew J. Redox Biology, Vol. 17 https://doi.org/10.1016/j.redox.2018.05.011	journal	July 2018
Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases Kehm, Richard; Baldensperger, Tim; Raupbach, Jana Redox Biology, Vol. 42 https://doi.org/10.1016/j.redox.2021.101901	journal	June 2021
Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging McDonagh, Brian; Sakellariou, Giorgos K.; Smith, Neil T. Journal of Proteome Research, Vol. 13, Issue 11 https://doi.org/10.1021/pr5006394	journal	September 2014
A common nonsense mutation results in α-actinin-3 deficiency in the general population North, Kathryn N.; Yang, Nan; Wattanasirichaigoon, Duangrurdee Nature Genetics, Vol. 21, Issue 4 https://doi.org/10.1038/7675	journal	April 1999
Resin-assisted enrichment of thiols as a general strategy for proteomic profiling of cysteine-based reversible modifications Guo, Jia; Gaffrey, Matthew J.; Su, Dian Nature Protocols, Vol. 9, Issue 1 https://doi.org/10.1038/nprot.2013.161	journal	December 2013
Hypertrophic cardiomyopathy mutations in the calponin-homology domain of ACTN2 affect actin binding and cardiomyocyte Z-disc incorporation Haywood, Natalie J.; Wolny, Marcin; Rogers, Brendan Biochemical Journal, Vol. 473, Issue 16 https://doi.org/10.1042/bcj20160421	journal	August 2016
Thiol-Based Redox Switches in Eukaryotic Proteins Brandes, Nicolas; Schmitt, Sebastian; Jakob, Ursula Antioxidants & Redox Signaling, Vol. 11, Issue 5 https://doi.org/10.1089/ars.2008.2285	journal	May 2009
The sva package for removing batch effects and other unwanted variation in high-throughput experiments Leek, Jeffrey T.; Johnson, W. Evan; Parker, Hilary S. Bioinformatics, Vol. 28, Issue 6 https://doi.org/10.1093/bioinformatics/bts034	journal	January 2012
The interaction of titin and alpha-actinin is controlled by a phospholipid-regulated intramolecular pseudoligand mechanism Young, P. The EMBO Journal, Vol. 19, Issue 23 https://doi.org/10.1093/emboj/19.23.6331	journal	December 2000
Mitochondrial Energetics in Skeletal Muscle Are Associated With Leg Power and Cardiorespiratory Fitness in the Study of Muscle, Mobility and Aging Mau, Theresa; Lui, Li-Yung; Distefano, Giovanna The Journals of Gerontology: Series A, Vol. 78, Issue 8 https://doi.org/10.1093/gerona/glac238	journal	December 2022
The Study of Muscle, Mobility and Aging (SOMMA): A Unique Cohort Study About the Cellular Biology of Aging and Age-related Loss of Mobility Cummings, Steven R.; Newman, Anne B.; Coen, Paul M. The Journals of Gerontology: Series A, Vol. 78, Issue 11 https://doi.org/10.1093/gerona/glad052	journal	February 2023
Aging: A Theory Based on Free Radical and Radiation Chemistry Harman, D. Journal of Gerontology, Vol. 11, Issue 3 https://doi.org/10.1093/geronj/11.3.298	journal	July 1956
Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance Xirouchaki, Chrysovalantou E.; Jia, Yaoyao; McGrath, Meagan J. Science Advances, Vol. 7, Issue 51 https://doi.org/10.1126/sciadv.abl4988	journal	December 2021
Characterization of cellular oxidative stress response by stoichiometric redox proteomics Zhang, Tong; Gaffrey, Matthew J.; Li, Xiaolu American Journal of Physiology-Cell Physiology, Vol. 320, Issue 2 https://doi.org/10.1152/ajpcell.00040.2020	journal	February 2021
S-nitrosylation andS-glutathionylation of Cys134 on troponin I have opposing competitive actions on Ca²⁺sensitivity in rat fast-twitch muscle fibers Dutka, T. L.; Mollica, J. P.; Lamboley, C. R. American Journal of Physiology-Cell Physiology, Vol. 312, Issue 3 https://doi.org/10.1152/ajpcell.00334.2016	journal	March 2017
Type II skeletal myofibers possess unique properties that potentiate mitochondrial H ₂ O ₂ generation Anderson, Ethan J.; Neufer, P. Darrell American Journal of Physiology-Cell Physiology, Vol. 290, Issue 3 https://doi.org/10.1152/ajpcell.00402.2005	journal	March 2006
Oxidation alters myosin-actin interaction and force generation in skeletal muscle filaments Elkrief, Daren; Cheng, Yu-Shu; Matusovsky, Oleg S. American Journal of Physiology-Cell Physiology, Vol. 323, Issue 4 https://doi.org/10.1152/ajpcell.00427.2021	journal	October 2022
Rat bronchoalveolar lavage proteome changes following e-cigarette aerosol exposures Day, Nicholas J.; Wang, Juan; Johnston, Carl J. American Journal of Physiology-Lung Cellular and Molecular Physiology, Vol. 324, Issue 5 https://doi.org/10.1152/ajplung.00016.2023	journal	May 2023
ACTN3 (R577X) genotype is associated with fiber type distribution Vincent, Barbara; De Bock, Katrien; Ramaekers, Monique Physiological Genomics, Vol. 32, Issue 1 https://doi.org/10.1152/physiolgenomics.00173.2007	journal	December 2007
Accessibility of Myofilament Cysteines and Effects on ATPase Depend on the Activation State during Exposure to Oxidants Gross, Sean M.; Lehman, Steven L. PLoS ONE, Vol. 8, Issue 7 https://doi.org/10.1371/journal.pone.0069110	journal	July 2013
The Measurement of Reversible Redox Dependent Post-translational Modifications and Their Regulation of Mitochondrial and Skeletal Muscle Function Kramer, Philip A.; Duan, Jicheng; Qian, Wei-Jun Frontiers in Physiology, Vol. 6 https://doi.org/10.3389/fphys.2015.00347	journal	November 2015
ACTN3: More than Just a Gene for Speed Pickering, Craig; Kiely, John Frontiers in Physiology, Vol. 8 https://doi.org/10.3389/fphys.2017.01080	journal	December 2017
Stoichiometric Thiol Redox Proteomics for Quantifying Cellular Responses to Perturbations Day, Nicholas J.; Gaffrey, Matthew J.; Qian, Wei-Jun Antioxidants, Vol. 10, Issue 3 https://doi.org/10.3390/antiox10030499	journal	March 2021
Exercise-Stimulated ROS Sensitive Signaling Pathways in Skeletal Muscle Bouviere, Jessica; Fortunato, Rodrigo S.; Dupuy, Corinne Antioxidants, Vol. 10, Issue 4 https://doi.org/10.3390/antiox10040537	journal	March 2021
Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2 Rodriguez Garcia, Michelle; Schmeckpeper, Jeffrey; Landim-Vieira, Maicon International Journal of Molecular Sciences, Vol. 24, Issue 19 https://doi.org/10.3390/ijms241914572	journal	September 2023
Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension Musci, Robert; Hamilton, Karyn; Linden, Melissa Sports, Vol. 7, Issue 7 https://doi.org/10.3390/sports7070170	journal	July 2019

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Title: 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)

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References (37)

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