ArticlePloS one2012
Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 242 citations in OpenAlex.
- AChRs Degeneration at NMJ in Aging-Associated Sarcopenia-A Systematic Review.Frontiers in aging neuroscience · 2020Pooled it
- Trial
- Age-Associated Changes in the Spectral and Statistical Parameters of Surface Electromyogram of Tibialis Anterior.BioMed research international · 2016Trial
- The hallmarks of skeletal muscle health.Nature metabolism · 2026Review
- Review
- Treating age-related loss of muscle mass and function: Where should we be focusing?The Journal of physiology · 2026Review
- Hypoglossal and lumbar motor neuron death in old Sprague-Dawley rats.Physiological reports · 2026Article
- Muscle fibre denervation in ageing.Clinical science (London, England : 1979) · 2026Review
- Fiber type specific tibialis anterior muscle atrophy and oxidative capacity reduction is contemporaneous with death of larger lumbar motor neurons in old rats.Physiological reports · 2026Article
- The evidence for old age motor neuron death: A scoping review.Physiological reports · 2026Article
- Article
- Lysophosphatidic acid mediates skeletal muscle fibrosis in denervation via activation of YAP/TAZ.JCI insight · 2026Article
- Entropy of Muscle Fiber Histology Predicts Mobility in Older Adults: The Study of Muscle, Mobility, and Aging.Aging cell · 2026Article
- Molecular interaction mechanisms of muscle fiber type transition in aging sarcopenia and the role of exercise intervention.The Egyptian journal of internal medicine · 2026Article
- Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.International journal of molecular sciences · 2025Article
- The Neuromuscular Junction: A Shared Vulnerability in Aging and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- O-GlcNAcase Inhibitor Improves Denervation-Induced Muscle Atrophy in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Episodic denervation as a driver of loss of skeletal muscle redox homeostasis and muscle weakness in sarcopenia: Possible amelioration by exercise.Sports medicine and health science · 2025Review
- Redox-regulated signalling of adaptations to contractile activity in skeletal muscle: Implications for age-related muscle weakness.Experimental physiology · 2025Review
- Early nanoparticle intervention preserves motor function following cervical spinal cord injury.Bioengineering & translational medicine · 2025Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
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±34 MNs×mm⁻¹) and SEN (469±13 MNs×mm⁻¹). Nav₁.₅ positive fibers (1548±70 μm²) were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05) in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05) where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05), consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.