ArticleCell death discovery2023
TNF-α contributes to sarcopenia through caspase-8/caspase-3/GSDME-mediated pyroptosis.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Scientific landscape of oxidative stress in sarcopenia: from bibliometric analysis to hotspots review.Frontiers in medicine · 2024Pooled it
- Modulation of inflammasome components in patients with heart failure using oral nutritional supplements: investigating the molecular mechanisms beyond the clinical benefit.European journal of nutrition · 2026Trial
- Trial
- Pyroptosis as a novel therapeutic target in glioblastoma multiforme: Mechanisms, molecular insights, and therapeutic potential.Molecular therapy. Nucleic acids · 2026Review
- Article
- Gasdermin-Mediated Pyroptosis: Novel Strategies Against Colorectal Cancer.Cancer science · 2026Review
- Imeglimin Attenuates Skeletal Muscle Atrophy in Mouse Models of Obesity and Ageing.Journal of cachexia, sarcopenia and muscle · 2026Article
- The association between low skeletal muscle mass and immunoinflammatory markers in middle-aged and elderly patients with type 2 diabetes mellitus.Irish journal of medical science · 2026Article
- Bat-Inspired Longevity: Immune Damage Management and Nutritional Modulation for Healthy Aging.International journal of molecular sciences · 2026Review
- Review
- Article
- Single nuclei/cell transcriptomics reveal DMD driven cell dynamics and mechanisms of fibroblast inflammatory tissue priming in human dystrophic muscle.Research square · 2026Article
- Association of inflammatory biomarkers with physical and cognitive frailty in a Spanish population of older adults.GeroScience · 2026Article
- Inflammaging-induced TRAF3 degradation impairs AMP biosynthesis to drive sarcopenia.Research square · 2026Article
- Eupatorium perfoliatum Counteracts TNF-α Mediated Pathogenesis in Chikungunya Virus Infection.Applied biochemistry and biotechnology · 2026Article
- Is Ferroptosis the Mechanistic Bridge Connecting Iron Dysregulation to Muscle Wasting and Functional Decline in Aging?Aging cell · 2026Review
- MircoRNAs as regulators of regulated cell death in cancer progression: a focus on ferroptosis, anoikis and pyroptosis.Frontiers in pharmacology · 2026Review
- Convergent innate immune and regulated cell-death pathways in selected myopathies.Frontiers in immunology · 2026Review
- Sarcopenia and sepsis fuel a self-perpetuating cycle of immunometabolism decline.Frontiers in immunology · 2026Review
- Elevated Inflammatory Burden Index Is Association With Increased Sarcopenia: A Population-Based Study.Mediators of inflammation · 2026Article
14 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
10 authors at 1 institution in 1 country.
Funding
Abstract
Sarcopenia has become a leading cause of disability and mortality in the elderly. It has been reported that programmed cell death (PCD) is associated with the development of sarcopenia that is characterized by reduction of muscle fiber size and number. TNF-α is also validated to play a prominent role in sarcopenia through its complex signaling pathways including cell death signaling. However, it is still unclear whether TNF-α contributes to sarcopenia by mediating pyroptosis, one type of PCD. Here, we first established naturally aged mice with sarcopenia model and confirmed an inflammatory state represented by TNF-α in aged mice. Evidence of GSDME-mediated pyroptosis and activation of apoptotic caspase-8/-3 were also found in skeletal muscle cells of aged mice with sarcopenia. We demonstrated that TNF-α triggered GSDME-mediated pyroptosis in myotubes through activating caspase-8 and caspase-3 by using caspase-8 and caspase-3 inhibitors. Comparing the activation of caspase-8 and GSDME expression between TNF Complex IIa and TNF Complex IIb, TNF-α was found to be more inclined to assemble TNF Complex IIb in activating caspase-8 and triggering pyroptosis. Moreover, pyroptotic myotubes were validated to result in decreased expression of MHC1 and finally loss of myotubes by knockdown of GSDME. Our work reveals a novel mechanism that TNF-ɑ/caspase-8/caspase-3/GSDME signaling-mediated pyroptosis contributes to the development of sarcopenia. Caspase-3/GSDME signaling-mediated pyroptosis may be a promising therapeutic target for sarcopenia.
Identifiers
What OpenQuestion holds
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.