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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Uncoupled inflammatory, proliferative, and cytoskeletal responses in senescent human gingival fibroblasts.
Jassir Páez,Romina Hernández,Javier Espinoza,Leticia Rojas,Constanza Martínez,Nicolás Tobar,Jorge Martínez,Patricio C. Smith +7 more
TL;DR: The results imply that cytoskeletal changes and inhibition of cell proliferation represent early modifications in the structure and function of senescent gingival fibroblasts that are not coupled with the acquisition of an inflammatory phenotype.
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Effects of childhood exposure to PM2.5 in a Memphis pediatric asthma cohort
TL;DR: Investigation of individual-level associations between asthma and exposure measures in high asthma rate and low asthma rate areas and factors that influence asthma at first year of a child’s life, first 2 years, first 5 years, and during their childhood can guide efforts to minimize emissions, manage risk, and design interventions to reduce disease burden.
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Hyaluronan: A key player or just a bystander in skin photoaging?
TL;DR: In this paper, an overview of the literature concerning the changes in hyaluronan amount, size and metabolism, and the potential role of HA in photoaging is provided, as well as novel HA contributions to photoaging.
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Targeting cellular senescence in cancer by plant secondary metabolites: A systematic review
TL;DR: A recent systematic review highlights the critical roles of natural secondary metabolites in the attenuation of autocrine and paracrine cellular senescence pathways, while also elucidating the chemopreventive and chemotherapeutic capabilities of these compounds as discussed by the authors.
Journal ArticleDOI
A Senescence Bystander Effect in Human Lung Fibroblasts.
David W Waters,David W Waters,Michael Schuliga,Prabuddha S. Pathinayake,Lan Wei,Hui Ying Tan,Kaj E C Blokland,Kaj E C Blokland,Kaj E C Blokland,Jade Jaffar,Glen P. Westall,Janette K. Burgess,Cecilia M. Prêle,Steven E. Mutsaers,Christopher Grainge,Darryl A. Knight,Darryl A. Knight,Darryl A. Knight +17 more
TL;DR: In this paper, the authors investigated whether senescent human lung fibroblasts and alveolar epithelial cells (AECs) could induce a senescent-like phenotype in "naive" non-senescent LFs in vitro.
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