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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TGF-β Family Signaling in the Control of Cell Proliferation and Survival
TL;DR: The current understanding and recent progress on the biological effects of TGF-β at the cellular level are reviewed, with the hope of providing a framework for understanding how cells respond to T GF-β signals in specific contexts, and why disruption of such mechanisms may result in different human diseases including cancer.
Journal ArticleDOI
Identification of Senescent Cells in the Bone Microenvironment
Joshua N. Farr,Daniel G. Fraser,Haitao Wang,Katharina Jaehn,Mikolaj Ogrodnik,Megan M. Weivoda,Matthew T. Drake,Tamara Tchkonia,Nathan K. LeBrasseur,James L. Kirkland,Lynda F. Bonewald,Robert J. Pignolo,David G. Monroe,Sundeep Khosla +13 more
TL;DR: Data show that with aging, a subset of cells of various lineages within the bone microenvironment become senescent, although senescent myeloid cells and senescent osteocytes predominantly develop the senescence‐associated secretory phenotype.
Journal ArticleDOI
Measuring biological aging in humans: A quest.
Luigi Ferrucci,Marta Gonzalez-Freire,Elisa Fabbri,Elisa Fabbri,Eleanor M. Simonsick,Toshiko Tanaka,Zenobia A. Moore,Shabnam Salimi,Felipe Sierra,Rafael de Cabo +9 more
TL;DR: Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging.
Journal ArticleDOI
Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis
Mikolaj Ogrodnik,Mikolaj Ogrodnik,Yi Zhu,Larissa G.P. Langhi,Tamar Tchkonia,Patrick Krüger,Edward Fielder,Stella Victorelli,Rifqha A. Ruswhandi,Nino Giorgadze,Tamar Pirtskhalava,Oleg Podgorni,Grigori Enikolopov,Kurt O. Johnson,Ming Xu,Christine Inman,Allyson K. Palmer,Marissa J. Schafer,Moritz Weigl,Yuji Ikeno,Terry C. Burns,João F. Passos,João F. Passos,Thomas von Zglinicki,Thomas von Zglinicki,James L. Kirkland,Diana Jurk,Diana Jurk +27 more
TL;DR: It is found that obesity results in the accumulation of senescent glial cells in proximity to the lateral ventricle, a region in which adult neurogenesis occurs, and that senolytics are a potential new therapeutic avenue for treating neuropsychiatric disorders.
Journal ArticleDOI
Senescence-associated inflammatory responses: aging and cancer perspectives
Audrey Lasry,Yinon Ben-Neriah +1 more
TL;DR: It is proposed that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases.
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