ArticleAging cell2024
The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed.
- Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.Biogerontology · 2026Review
- Layer-Specific Dermal and Subcutaneous Delivery via Modular LNP-Hydrogel-Integrated Threaded Microneedles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Terpenoids as modulators of autophagy-senescence crosstalk in lung cancer.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Review
- STING expression in pituitary neuroendocrine tumour immune microenvironments.Endocrine-related cancer · 2026Article
- Effect of Ketogenic Diet Versus Vegan Diet on Obesity-Induced Testicular Dysfunction and Mediating Role of Gut Microbiota.International journal of molecular sciences · 2026Article
- Synergistic senolytic-regenerative therapy significantly extends healthspan and lifespan.Journal of translational medicine · 2026Article
- Advanced drug delivery platforms targeting cellular senescence: A promising strategy for cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Article
- Inhibition of MyD88 in Tubular Epithelial Cells Alleviates the Cellular Senescence in Sepsis-Associated Acute Kidney Injury.Inflammation · 2026Article
- Extracellular cGAMP in health and disease.Molecular biomedicine · 2026Review
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.Inflammation and regeneration · 2026Review
- Endothelial cell senescence shapes T cell activity in late-stage of chronic obstructive pulmonary disease.Cell death discovery · 2026Article
- Astrocyte States in Brain Aging and Neurodegeneration: At the Crossroads of Senescence and Reactivity.Neurochemical research · 2026Review
- cGAS-STING signaling in pollution-induced toxicity: mechanism and relieving medication.Apoptosis : an international journal on programmed cell death · 2026Review
- Unraveling skeletal muscle senescence in anFrontiers in aging · 2026Article
- Baicalin alleviates uterine inflammaging and improves eggshell quality in aged laying hens.Frontiers in immunology · 2026Article
- Research advances and application prospects of CAR-T therapy in the treatment of age-related diseases.Frontiers in immunology · 2026Review
- Cellular senescence in cancer immunology and potential therapeutic strategy.Frontiers in oncology · 2026Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Senescent cells produce a Senescence-Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin-6 (IL-6), has the potential to amplify cellular senescence in the SASP-producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear. We found that the senescence action does not involve IL-6 secretion nor the interaction with the receptor expressed in the membrane but is amplified through an intracrine mechanism. IL-6 sustains intracrine senescence interacting with the intracellular IL-6 receptor located in anterograde traffic specialized structures, with cytosolic DNA, cGAS-STING, and NFκB activation. This pathway triggered by intracellular IL-6 significantly contributes to cell-autonomous induction of senescence and impacts in tumor growth control. Inactivation of IL-6 in somatotrophic senescent cells transforms them into strongly tumorigenic in NOD/SCID mice, while re-expression of IL-6 restores senescence control of tumor growth. The intracrine senescent IL-6 pathway is further evidenced in three human cellular models of therapy-induced senescence. The compartmentalization of the intracellular signaling, in contrast to the paracrine tumorigenic action, provides a pathway for IL-6 to sustain cell-autonomous senescent cells, driving the SASP, and opens new avenues for clinical consideration to senescence-based therapies.
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