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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Senescent skeletal cells cross-talk with synovial cells plays a key role in the pathogenesis of osteoarthritis
Chongjie Wu,Ri Liu,Songwei Huan,Wang Tang,Yuzhe Zeng,Jun-cheng Zhang,Jie Yang,Zhen-Yan Li,Ying Zhou,Zhengang Zha,Juan Zhang,Ning Liu +11 more
TL;DR: The role of the senescent skeletal cells (chondrocytes, osteoblasts, osteocyte, and muscle cells) in initiating the development and progression of osteoarthritis alone or through cross-talk with the macrophages/synovial cells is discussed in this paper .
Journal ArticleDOI
X-ray irradiation accelerates senescence in hippocampal neural stem/progenitor cells via caspase-1 activation
TL;DR: It is demonstrated that X-ray irradiation may inhibit proliferation, induce senescence of NSPCs through caspase-1 activation, and suggest that caspasin activation is involved in irradiation-induced damage to N SPCs.
Journal ArticleDOI
Senolytic treatment reduces cell senescence and necroptosis in Sod1 knockout mice that is associated with reduced inflammation and hepatocellular carcinoma
Nidheesh Thadathil,Ramasamy Selvarani,Sabira Mohammed,Evan H Nicklas,Albert L. Tran,Maria Kamal,Wenyi Luo,Jacob D. Brown,Marcus M. Lawrence,Agnieszka Borowik,Benjamin F. Miller,Holly Van Remmen,Arlan Richardson,Sathyaseelan S. Deepa +13 more
TL;DR: It is proposed that these two cell fates interact through a positive feedback loop resulting in a cycle amplifying both cellular senescence and necroptosis leading to inflammaging and age-associated pathology in the Sod1KO mice.
Journal ArticleDOI
Tendon Extracellular Matrix Assembly, Maintenance and Dysregulation Throughout Life.
Seyed Mohammad Siadat,Danae E Zamboulis,Chavaunne T. Thorpe,Jeffrey W. Ruberti,Brianne K Connizzo +4 more
TL;DR: The tendon extracellular matrix (ECM) is critical to overall tissue function and it gives the tissue its unique mechanical properties, exhibiting complex non-linear responses, viscoelasticity and flow mechanisms, excellent energy storage and fatigue resistance as discussed by the authors.
Journal ArticleDOI
MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Redox Control of Cell Senescence
Daniele Lettieri-Barbato,Katia Aquilano,Carolina Punziano,Giuseppina Minopoli,Raffaella Faraonio +4 more
TL;DR: Recent data on the link between ROS/RNS-induced senescence and the current knowledge on the role of non-coding RNAs in thesenescence program are described.
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