ArticleAging2017
TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion.
Article in Aging, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Cellular senescence and chronological age in various human tissues: A systematic review and meta-analysis.Aging cell · 2020Pooled it
- Article
- Effects and Therapeutic Strategies of Intra-Hepatic Cellular Senescence and Regeneration.International journal of molecular sciences · 2026Review
- Age-associated Autoimmunity Driven by T cell Immunosenescence.bioRxiv : the preprint server for biology · 2026Article
- Quantitative proteomics reveals coordinated changes in the proteome during replicative senescence.Nature communications · 2026Article
- TRF2 enriched cytoplasmic chromatin drives cGAS-STAT1-mediated inflammation in senescence.iScience · 2026Article
- Inhibition of inflammation and senescence with azole compound C7 enables expansion of hematopoietic stem and progenitor cells.Stem cells translational medicine · 2026Article
- Comprehensive analysis to develop a stromal senescence-associated gene signature for predicting hepatocellular carcinoma.Translational cancer research · 2026Article
- Elimination of senescent cells with senolytic drugs as adjunctive host-directed therapy reduces tuberculosis progression in mice.Nature communications · 2026Article
- Elucidation of a potent pro-resolving mediator of inflammation resolution via human neutrophil-vascular endothelial cell interactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy.Cell death & disease · 2026Article
- Necroptosis-senescence crosstalk in tubulointerstitial fibrosis: the mtDNA-cGAS-STING-PFKFB3 axis as a metabolic bridge.Frontiers in medicine · 2026Review
- Article
- Endothelial senescent-cell-specific clearance alleviates metabolic dysfunction in obese mice.Cell metabolism · 2025Article
- The multifaceted role of lactate in cardiovascular health: from metabolism to signaling and epigenetics.Epigenetics · 2025Review
- Tissue specificity and chromosomal alterations shape divergent immune programs in HRD tumors.bioRxiv : the preprint server for biology · 2025Article
- Comparative serum proteomics of plasmodium-infected free-living macaques in Thailand: Host immune responses and candidate biomarkers for zoonotic malaria.Veterinary world · 2025Article
- Article
- The states of senescent cells.Biochemical Society transactions · 2025Review
- Tabula Sapiens reveals transcription factor expression, senescence effects, and sex-specific features in cell types from 28 human organs and tissues.bioRxiv : the preprint server for biology · 2025Article
44 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
Cellular senescence is a cell fate program that entails essentially irreversible proliferative arrest in response to damage signals. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some types of senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways linking TNFα-related inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that TNFα induces permanent growth arrest and increases p21CIP1, p16INK4A, and SA-β-gal, accompanied by persistent DNA damage and ROS production. By gene expression profiling, we identified the crucial involvement of inflammatory and JAK/STAT pathways in TNFα-mediated senescence. We found that TNFα activates a STAT-dependent autocrine loop that sustains cytokine secretion and an interferon signature to lock cells into senescence. Furthermore, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from proliferative arrest, but rather suppressed cell cycle regulatory genes and altered TNFα-induced senescence. Our findings suggest a positive feedback mechanism via the STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
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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.