Age-related Differences in Dystrophin: Impact on Force Transfer Proteins, Membrane Integrity, and Neuromuscular Junction Stability

作者：Hughes David C; Marcotte George R; Marshall Andrea G; West Daniel W D; Baehr Leslie M; Wallace Marita A; Saleh Perrie M; Bodine Sue C; Baar Keith

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2017, 72(5): 640-648.

DOI：10.1093/gerona/glw109

• Force transmission
• Skeletal muscle
• Dystrophin-associated glycoprotein complex
• Aging
• Regeneration

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.

• 出版日期2017-5