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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Aberrant signaling and senescence associated protein degradation
TL;DR: The evidence supporting a general role for aberrant signaling and senescence associated protein degradation for organismal aging is discussed.
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Hypoxia-inducible factor-2α mediates senescence-associated intrinsic mechanisms of age-related bone loss
Sun Young Lee,Ka Hyon Park,Gyuseok Lee,Su-Jin Kim,Won-Hyun Song,Seung-Hee Kwon,Jeong-Tae Koh,Yun Hyun Huh,Je-Hwang Ryu +8 more
TL;DR: In this article, HIF-2α expression was shown to be highly upregulated in aged bones, indicating that HIF2α upregulation in senescent osteoblasts may be a result of aging rather than a cause of cellular senescence.
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Role of Complement in Regulating Inflammation Processes in Renal and Prostate Cancers
Giuseppe Stefano Netti,Rossana Franzin,Alessandra Stasi,Federica Spadaccino,Andrea Dello Strologo,Barbara Infante,Loreto Gesualdo,Giuseppe Castellano,Elena Ranieri,Giovanni Stallone +9 more
TL;DR: In this paper, the authors discuss the role of cellular senescence in cancer with a particular focus on tumors that are strongly dependent on complement activation and can be understood by a new, Senescence-related point of view: prostate cancer and renal cell carcinoma.
Dissertation
Ejercicio y envejecimiento: cambios transcripcionales y epigenéticos en un modelo murino de envejecimiento acelerado
Álvarez López,Maria Jesús +1 more
TL;DR: In particular, this paper found that ratones SAMP8 showed an increase in histona H3 trimetilada in lisina 4 in linfocitos, hipocampo and corteza cerebral.
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p53 loss does not permit escape from BrafV600E-induced senescence in a mouse model of lung cancer.
TL;DR: It is shown that p53 loss before OIS is permissive for the transition from lung adenoma to adenocarcinoma, and that therapy-induced senescence would halt further tumor progression.
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