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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NK cells generate memory-type responses to human cytomegalovirus-infected fibroblasts.
TL;DR: Comparisons of proliferation, natural cytotoxicity and interferon‐γ (IFN‐γ) production of NK cells from HCMV‐seropositive and HCMVs‐seronegative individuals co‐cultured with HCMv‐infected or uninfected MRC‐5 cells illustrate an at least partly NKG2C‐independent human NK‐cell memory‐type response against H CMV.
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NF-κB/IKK activation by small extracellular vesicles within the SASP
Juan Fafián-Labora,Ana O'Loghlen +1 more
TL;DR: In this paper, the authors performed a small molecule inhibitor screen and identified the IκB kinases IKKe, IKKα and IKKβ as essential for senescence mediated by extracellular vesicles.
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Telomere damage promotes vascular smooth muscle cell senescence and immune cell recruitment after vessel injury.
Anna K. Uryga,Mandy O.J. Grootaert,Abel Martin Garrido,Sebnem Oc,Kirsty Foote,Joel Chappell,Alison Finigan,Francesca Rossiello,Fabrizio d'Adda di Fagagna,Dimitra Aravani,Helle F. Jørgensen,Martin R. Bennett +11 more
TL;DR: Uryga et al. as discussed by the authors showed that stress-induced premature senescence (SIPS) and stable expression of a telomeric repeat-binding factor 2 protein mutant (TRF2T188A) induce senesence of human vascular smooth muscle cells (VSMCs), associated with persistent DNA damage.
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Diabetes-Induced Cellular Senescence and Senescence-Associated Secretory Phenotype Impair Cardiac Regeneration and Function Independently of Age.
Fabiola Marino,Maria Teresa Scalise,Nadia Salerno,Luca Salerno,Claudia Molinaro,Donato Cappetta,Michele Torella,M. Greco,Daniela Foti,Ferdinando Carlo Sasso,Pasquale Mastroroberto,Antonella De Angelis,Georgina M. Ellison-Hughes,Maurilio Sampaolesi,Marcello Rota,Francesco Rossi,Konrad Urbanek,Bernardo Nadal-Ginard,Daniele Torella,Eleonora Cianflone +19 more
TL;DR: DM hampers CSC biology inhibiting their regenerative potential through the induction of cellular senescence and SASP independently from aging.
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Size-scaling promotes senescence-like changes in proteome and organelle content
TL;DR: In this paper, the authors used proteomic data from 59 unperturbed human cell lines to systematically characterize cell-size dependent changes in intracellular protein concentrations and organelle content.
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