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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Cell Senescence: A Nonnegligible Cell State under Survival Stress in Pathology of Intervertebral Disc Degeneration.
Zhang Yu'ang,Biao Yang,Jingkai Wang,Feng Cheng,Kesi Shi,Liwei Ying,Chenggui Wang,Kaishun Xia,Xianpeng Huang,Zhe Gong,Chao Yu,Fangcai Li,Chengzhen Liang,Qixin Chen +13 more
TL;DR: Another important cell state apart from cell death in IDD is clarified and senescence-associated changes in cells and extracellular microenvironment are discussed, which emphasize the role of oxidative stress and epigenomic perturbations in linking risk factors to cellsenescence in the onset of IDD.
Journal ArticleDOI
The Emerging Role of Senescence in Ocular Disease.
TL;DR: There is reasonable evidence that senescence could be a modifiable factor, and hence, it may be possible to delay age-related diseases by modulating basic aging mechanisms using SASP inhibitors/senolytic drugs, and antisenescent therapies in aging and age- related diseases appear to have a promising potential.
Journal ArticleDOI
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence.
Ioana Olan,Aled Parry,Aled Parry,Stefan Schoenfelder,Masako Narita,Yoko Ito,Adelyne S. L. Chan,Guy Slater,Dóra Bihary,Masashige Bando,Katsuhiko Shirahige,Hiroshi Kimura,Shamith A. Samarajiwa,Peter Fraser,Peter Fraser,Masashi Narita,Masashi Narita +16 more
TL;DR: It is suggested that RAS-induced senescence represents a cell fate determination-like process characterised by a unique gene expression profile and 3D genome folding signature, mediated in part through cohesin redistribution on chromatin.
Journal ArticleDOI
The Paradoxical Role of Cellular Senescence in Cancer.
TL;DR: In this paper, the authors performed a review to summarize both bright and dark sides of senescence in cancer, and the strategies to handle senescent cells in cancer therapy were also discussed.
Journal ArticleDOI
Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma.
Qinchao Hu,Jianmin Peng,Laibo Jiang,Wuguo Li,Qiao Su,Jiayu Zhang,Huan Li,Ming Song,Bin Cheng,Juan Xia,Tong Wu +10 more
TL;DR: The data suggest that metformin can act as a senostatic drug to enhance the anticancer efficacy of CDK4/6 inhibitors by reprogramming the profiles of the SASP.
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