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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Bone marrow mesenchymal stem cells from patients with SLE maintain an interferon signature during in vitro culture.
Lin Gao,Mary J. O'Connell,Maria Allen,Jane L. Liesveld,Andrew McDavid,Jennifer H. Anolik,R J Looney +6 more
TL;DR: A subgroup of SLE BMSC is distinguished from other SLE patients and from controls by increased levels of mRNAs induced by type I interferons, and this sub group of Sle patients had increased Levels of IFNβ in vivo.
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Doxorubicin-induced senescence in normal fibroblasts promotes in vitro tumour cell growth and invasiveness: The role of Quercetin in modulating these processes
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Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults.
Breno S. Diniz,Breno S. Diniz,Érica Leandro Marciano Vieira,Ana Paula Mendes-Silva,Christopher R. Bowie,Christopher R. Bowie,Meryl A. Butters,Corinne E. Fischer,Corinne E. Fischer,Alastair J. Flint,Alastair J. Flint,Nathan Herrmann,Nathan Herrmann,James L. Kennedy,James L. Kennedy,Krista L. Lanctôt,Krista L. Lanctôt,Linda Mah,Bruce G. Pollock,Bruce G. Pollock,Benoit H. Mulsant,Benoit H. Mulsant,Tarek K. Rajji,Tarek K. Rajji +23 more
TL;DR: In this paper, the authors investigated whether molecular senescence changes in older adults are associated with a history of major depressive disorder (MDD) or mild cognitive impairment (MCI) or MCI.
Journal ArticleDOI
Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin
Matthew Mannarino,Hosni Cherif,Li Li,Kai Sheng,Kai Sheng,Oded Rabau,Oded Rabau,Peter Jarzem,Michael H. Weber,Jean Ouellet,Lisbet Haglund +10 more
TL;DR: It is demonstrated that activation of TLR-2/6 induce senescence and increase TLr-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and backpain and in cellsFrom degenerating human IVD of patients with disc degenerationand backpain.
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Molecular Mechanisms of Alveolar Epithelial Stem Cell Senescence and Senescence-Associated Differentiation Disorders in Pulmonary Fibrosis
TL;DR: Roles of alveolar epithelial stem cell senescence and senescences-associated differentiation disorders in pulmonary fibrosis are examined, exploring the mechanisms mediating and preventing pulmonary fibrogenic crisis and providing a framework for targeted intervention of the molecular mechanisms.
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