A complex secretory program orchestrated by the inflammasome controls paracrine senescence
Juan Carlos Acosta,Ana Banito,Torsten Wuestefeld,Athena Georgilis,Peggy Janich,Jennifer P. Morton,Dimitris Athineos,Tae-Won Kang,Felix Lasitschka,Mindaugas Andrulis,Gloria Pascual,Kelly J. Morris,Sadaf Khan,Hong Jin,Gopuraja Dharmalingam,Ambrosius P. Snijders,Thomas L. Carroll,David Capper,Catrin Pritchard,Gareth J. Inman,Thomas Longerich,Owen J. Sansom,Salvador Aznar Benitah,Lars Zender,Jesús Gil +24 more
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TLDR
It is demonstrated that the SASP can cause paracrine senescence and impact on tumour suppression andSenescence in vivo and TGF-β ligands play a major role by regulating p15INK4b and p21CIP1.Abstract:
Oncogene-induced senescence (OIS) is crucial for tumour suppression. Senescent cells implement a complex pro-inflammatory response termed the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence, activates immune surveillance and paradoxically also has pro-tumorigenic properties. Here, we present evidence that the SASP can also induce paracrine senescence in normal cells both in culture and in human and mouse models of OIS in vivo. Coupling quantitative proteomics with small-molecule screens, we identified multiple SASP components mediating paracrine senescence, including TGF-β family ligands, VEGF, CCL2 and CCL20. Amongst them, TGF-β ligands play a major role by regulating p15(INK4b) and p21(CIP1). Expression of the SASP is controlled by inflammasome-mediated IL-1 signalling. The inflammasome and IL-1 signalling are activated in senescent cells and IL-1α expression can reproduce SASP activation, resulting in senescence. Our results demonstrate that the SASP can cause paracrine senescence and impact on tumour suppression and senescence in vivo.read more
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Extracellular vesicles released from stress-induced prematurely senescent myoblasts impair endothelial function and proliferation.
Zachary R. Hettinger,Christopher K. Kargl,Jonathan H. Shannahan,Shihuan Kuang,Timothy P. Gavin +4 more
TL;DR: In this article, the impact of stress-induced premature senescence on skeletal muscle myoblast-derived extracellular vesicles (EVs) and myobblasts-endothelial cell crosstalk was investigated.
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The Impact of Polyphenols-Based Diet on the Inflammatory Profile in COVID-19 Elderly and Obese Patients
TL;DR: In this article, the pathogenesis and clinical implications of inflammatory disorders and disease markers associated to senescence in COVID-19 patients and the emerging evidence to argue that a high intake of polyphenols may have a protective effect on SARS-CoV-2 illness severity.
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A Comprehensive Overview of the Complex Role of Oxidative Stress in Aging, The Contributing Environmental Stressors and Emerging Antioxidant Therapeutic Interventions
TL;DR: Careful exposure to harmful environmental factors and the use of antioxidant supplements could potentially affect the biological processes driving aging and slow down the development of age-related diseases.
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Dynamic Aging: Channeled Through Microenvironment
TL;DR: In this article, a review discusses the mechanisms of how senescence and their secretome, NAD+ metabolism or circulating factors change microenvironments to regulate systematic aging, as well as the potential therapeutic strategies based on these findings for anti-aging interventions.
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AMPK alleviates oxidative stress‑induced premature senescence via inhibition of NF-κB/STAT3 axis-mediated positive feedback loop.
TL;DR: The results suggest that AMPK prevents oxidative stress-induced senescence development via inhibiting the NF-κB/SASP/STAT3 signalling mediated positive feedback loop.
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