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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Cellular Senescence: Pathogenic Mechanisms in Lung Fibrosis.
TL;DR: In this paper, a review describes regulatory pathways of cellular senescence and discusses the current knowledge on the cellular players of lung fibrosis, including epithelial cells (alveolar type 2 cells, basal cells, etc.), fibroblasts and immune cells, their phenotypic changes, and the cellular and molecular mechanisms by which these cells contribute to the pathogenesis of pulmonary fibrosis.
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Serum NT/CT SIRT1 ratio reflects early osteoarthritis and chondrosenescence.
George Batshon,Jinan Elayyan,Omar Qiq,Eli Reich,Louisa Ben-Aderet,Leonid Kandel,Amir Haze,J. Steinmeyer,Véronique Lefebvre,Hong Zhang,Jennifer H. Elisseeff,Yves Henrotin,Ali Mobasheri,Mona Dvir-Ginzberg +13 more
TL;DR: Increased levels of serum NT/CT SIRT1 ratio correlated with moderate OA in both mice and humans, stemming at least in part from non-senescent chondrocyte apoptosis, possibly a result of prolonged inflammatory insult.
Journal ArticleDOI
Modulators of cellular senescence: mechanisms, promises, and challenges from in vitro studies with dietary bioactive compounds.
Marco Malavolta,Laura Costarelli,Robertina Giacconi,Francesco Piacenza,Andrea Basso,Elisa Pierpaoli,Francesca Marchegiani,Maurizio Cardelli,Mauro Provinciali,Eugenio Mocchegiani +9 more
TL;DR: The evidence that various dietary bioactive compounds can modulate cellular senescence in vitro is discussed and findings and mechanisms that might be useful for the development of health-promoting nutraceuticals are summarized.
Journal ArticleDOI
Senescent cells and macrophages: key players for regeneration?
Sonia S. Elder,Elaine Emmerson +1 more
TL;DR: The role of macrophages and senescent cells in the regeneration and repair process following an injury has been investigated in this paper, where the authors consider the current literature regarding the interaction of these cell types, how their cooperation is important for regeneration, and what questions remain to be answered to advance the field.
Journal ArticleDOI
Cellular senescence in musculoskeletal homeostasis, diseases, and regeneration
TL;DR: In this article, the role of senescent cells in the maintenance of bone homeostasis during childhood and their contribution to the pathogenesis of chronic musculoskeletal disorders, including osteoporosis, osteoarthritis, and sarcopenia.
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