denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle去神经引起纤维萎缩,肌凝蛋白重链co-expression骨骼肌衰老.pdfVIP

Denervation Causes Fiber Atrophy and Myosin Heavy Chain Co-Expression in Senescent Skeletal Muscle 1 2 1 1 Sharon L. Rowan , Karolina Rygiel , Fennigje M. Purves-Smith , Nathan M. Solbak , Douglas M. 2 3 Turnbull , Russell T. Hepple * 1 Muscle and Aging Laboratory, Faculty of Kinesiology, University of Calgary, Calgary, Canada, 2 Mitochondrial Research Group, Institute for Ageing and Health, University of Newcastle Upon Tyne, Newcastle, United Kingdom, 3 Critical Care Division, Royal Victoria Hospital and Department of Medicine, McGill University, Montreal, Canada Abstract Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav1.5, in young adult (YA) and senescent (SEN) rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1). MN soma number in lumbar spinal cord declined 27% between YA (638 634 MNs 6mm21) and SEN (469 613 MNs6mm21). Nav1.5 positive fibers (1548670 mm2 2 ) were 35% smaller than Nav1.5 negative fibers (2367678 mm ; P,0.05) in SEN muscle, whereas Nav1.5