Journal article
Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability
The journals of gerontology. Series A, Biological sciences and medical sciences, Vol.72(5), pp.640-648
05/01/2017
DOI: 10.1093/gerona/glw109
PMCID: PMC5861877
PMID: 27382038
Abstract
The loss of muscle strength with age has been studied from the perspective of a decline in muscle mass and neuromuscular junction (NMJ) stability. A third potential factor is force transmission. The purpose of this study was to determine the changes in the force transfer apparatus within aging muscle and the impact on membrane integrity and NMJ stability. We measured an age-related loss of dystrophin protein that was greatest in the flexor muscles. The loss of dystrophin protein occurred despite a twofold increase in dystrophin mRNA. Importantly, this disparity could be explained by the four-to fivefold upregulation of the dystromir miR-31. To compensate for the loss of dystrophin protein, aged muscle contained increased alpha-sarcoglycan, syntrophin, sarcospan, laminin, beta 1-integrin, desmuslin, and the Z-line proteins alpha-actinin and desmin. In spite of the adaptive increase in other force transfer proteins, over the 48 hours following lengthening contractions, the old muscles showed more signs of impaired membrane integrity (fourfold increase in immunoglobulin G-positive fibers and 70% greater dysferlin mRNA) and NMJ instability (14- to 96-fold increases in Runx1, AchRd, and myogenin mRNA). Overall, these data suggest that age-dependent alterations in dystrophin leave the muscle membrane and NMJ more susceptible to contraction-induced damage even before changes in muscle mass are obvious.
Details
- Title: Subtitle
- Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability
- Creators
- David C. Hughes - Department of Neurobiology, Physiology and Behavior and.George R. Marcotte - Department of Neurobiology, Physiology and Behavior and.Andrea G. Marshall - University of California, DavisDaniel W. D. West - University of California, DavisLeslie M. Baehr - University of California, DavisMarita A. Wallace - Department of Neurobiology, Physiology and Behavior and.Perrie M. Saleh - Department of Neurobiology, Physiology and Behavior and.Sue C Bodine - University of California, DavisKeith Baar - University of California, Davis
- Resource Type
- Journal article
- Publication Details
- The journals of gerontology. Series A, Biological sciences and medical sciences, Vol.72(5), pp.640-648
- Publisher
- Oxford Univ Press
- DOI
- 10.1093/gerona/glw109
- PMID
- 27382038
- PMCID
- PMC5861877
- ISSN
- 1079-5006
- eISSN
- 1758-535X
- Number of pages
- 9
- Grant note
- I01RX000673 / Veterans Affairs; US Department of Veterans Affairs Natural Sciences and Engineering Research Council of Canada; Natural Sciences and Engineering Research Council of Canada (NSERC); CGIAR R01AG045375 / National Institute on Aging of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) VARR&D 1I01RX000673-01A1 / United States Department of Veterans Affairs; US Department of Veterans Affairs R01AG045375 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Language
- English
- Date published
- 05/01/2017
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359787002771
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