ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2020
TNF Receptor-Associated Factor 6 Mediates TNFα-Induced Skeletal Muscle Atrophy in Mice During Aging.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Biomarkers of Skeletal Muscle Atrophy Based on Atrogenes Evaluation: A Systematic Review and Meta-Analysis Study.International journal of molecular sciences · 2025Pooled it
- Proteomic Markers of Aging and Longevity: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Biomarkers of Cellular Senescence Predict the Onset of Mobility Disability and Are Reduced by Physical Activity in Older Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Trial
- Immunometabolic Remodeling in Osteosarcopenia: Inflammaging, Mitochondrial Dysfunction, Gut-Derived Metabolites and Therapeutic Opportunities.Metabolites · 2026Review
- Gan-Mai-Da-Zao-Tang attenuates age-induced skeletal muscle wasting and improves mitochondrial function in mice.Journal of traditional and complementary medicine · 2026Article
- A RANKLBone research · 2026Article
- Elevated serum TNF-α in patients with immune-mediated necrotizing myopathy correlates with muscle damage.BMC immunology · 2026Article
- Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inflammatory signaling and disruption of the histone H3.3 chromatin loading pathway.NAR molecular medicine · 2026Article
- Parthenolide Attenuates Skeletal Muscle Atrophy Through Regulation of Protein Homeostasis and Inhibition of Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Inflammaging-induced TRAF3 degradation impairs AMP biosynthesis to drive sarcopenia.Research square · 2026Article
- Transcending aging: disease specificity, assessment challenges, and management strategies for rheumatoid arthritis-related sarcopenia.Frontiers in medicine · 2026Review
- IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia.PloS one · 2026Article
- Correlation between the reduction of IL-6 and TNF-α with muscle mass restoration in hyperthyroid patients post-radioactive iodine therapy.Frontiers in endocrinology · 2026Article
- Exploring the potential targets and possible mechanisms of Shenqi Fuzheng Injection in the treatment of cancer-associated muscle wasting based on network pharmacology.Frontiers in genetics · 2026Article
- Combating muscle atrophy: emerging therapeutic targets that are fiber-type-specific.The FEBS journal · 2025Review
- TRAF6 regulates ubiquitination-independent TDP-43 condensation and related neurodegeneration.Molecular psychiatry · 2025Article
- Nrf2/Nlrp3 signaling in aging BMSCs: Traf6 intervention as a novel approach to osteoporosis treatment.Redox biology · 2025Article
- Article
- Analysis of the diagnostic accuracy of plasma sTNFr-2 concentrations in identifying sarcopenia in community-dwelling older women.Scientific reports · 2025Article
- Periarticular myositis and muscle fibrosis are cytokine-dependent complications of inflammatory arthritis.JCI insight · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
During aging, muscle mass decreases, leading to sarcopenia, associated with low-level chronic inflammation (inflammaging), which induces sarcopenia by promoting proteolysis of muscle fibers and inhibiting their regeneration. Patients with a variety of pathologic conditions associated with sarcopenia, including rheumatoid arthritis (RA), have systemically elevated TNFα serum levels, and transgenic mice with TNFα overexpression (TNF-Tg mice, a model of RA) develop sarcopenia between adolescence and adulthood before they age. However, if and how TNFα contributes to the pathogenesis of sarcopenia during the normal aging process and in RA remains largely unknown. We report that TNFα levels are increased in skeletal muscles of aged WT mice, associated with muscle atrophy and decreased numbers of satellite cells and Type IIA myofibers, a phenotype that we also observed in adult TNF-Tg mice. Aged WT mice also have increased numbers of myeloid lineage cells in their skeletal muscles, including macrophages and granulocytes. These cells have increased TNFα expression, which impairs myogenic cell differentiation. Expression levels of TNF receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, which mediates signaling by some TNF receptor (TNFR) family members, are elevated in skeletal muscles of both aged WT mice and adult TNF-Tg mice. TRAF6 binds to TNFR2 in C2C12 myoblasts and mediates TNFα-induced muscle atrophy through NF-κB-induced transcription of the muscle-specific E3 ligases, Atrogen1 and Murf1, which promote myosin heavy-chain degradation. Haplo-deficiency of TRAF6 prevents muscle atrophy and the decrease in numbers of satellite cells, Type IIA myofibers, and myogenic regeneration in TRAF6
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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.