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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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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Blue journal conference. Aging and susceptibility to lung disease.
Victor J. Thannickal,Mahadev Murthy,William E. Balch,Navdeep S. Chandel,Silke Meiners,Oliver Eickelberg,Moisés Selman,Annie Pardo,Eric S. White,Bruce D. Levy,Paula J. Busse,Rubin M. Tuder,Veena B. Antony,Jacob I. Sznajder,G. R. Scott Budinger +14 more
TL;DR: This article used the input gathered at the ATS meeting to develop a broad framework and perspective to stimulate basic, clinical, and translational research to understand how the aging process contributes to the onset and/or progression of lung diseases.
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Erdheim-Chester disease: a systematic review
Mauro Cives,Valeria Simone,Francesca Maria Rizzo,Franca Dicuonzo,Marirosa Cristallo Lacalamita,Giuseppe Ingravallo,Franco Silvestris,Franco Dammacco +7 more
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Cellular Senescence in Neurodegenerative Diseases.
Carmen Martínez-Cué,Noemí Rueda +1 more
TL;DR: The evidence of the shared neuropathological events in these neurodegenerative diseases and the implication of cellular senescence in their onset or aggravation are summarized.
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TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence
Thomas G. Bird,Thomas G. Bird,Miryam Müller,Luke Boulter,David F. Vincent,Rachel A. Ridgway,Elena Lopez-Guadamillas,Wei-Yu Lu,Thomas Jamieson,Olivier Govaere,Andrew D. Campbell,Sofia Ferreira-Gonzalez,Alicia M. Cole,Trevor Hay,Kenneth J. Simpson,William Clark,Ann Hedley,Mairi Clarke,Pauline Gentaz,Colin Nixon,Steven A. Bryce,Christos Kiourtis,Joep Sprangers,Robert J. B. Nibbs,Nico van Rooijen,Laurent Bartholin,Steven R. McGreal,Udayan Apte,Simon T. Barry,John P. Iredale,John P. Iredale,Alan Richard Clarke,Manuel Serrano,Tania Roskams,Owen J. Sansom,Stuart J. Forbes,Stuart J. Forbes +36 more
TL;DR: It is shown that a process that prevents proliferation termed senescence, which is classically associated with aging and carcinogenesis, inhibits the liver’s regenerative cells after acute injury, and is an attractive therapeutic target for developing treatments for acute liver failure.
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Cell cycle arrest and the evolution of chronic kidney disease from acute kidney injury
TL;DR: Recent advances in the understanding of the biology of the cell cycle and how cell cycle arrest links AKI to chronic kidney disease are summarized.
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