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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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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Identification of Salvia haenkei as gerosuppressant agent by using an integrated senescence-screening assay
Ivana Matic,Ajinkya Revandkar,Jingjing Chen,Angela Bisio,Stefano Dall'Acqua,Veronica Cocetta,Paola Brun,Giorgio Mancino,Martina Milanese,Maurizio Mattei,Monica Montopoli,Andrea Alimonti +11 more
TL;DR: A novel-screening assay is reported, for the identification of compounds that block different types of senescence response, and it is found that an extract from Salvia haenkei (SH), a native plant of Bolivia is a potent inhibitor of PICS.
Book ChapterDOI
Aging Biomarkers and Novel Targets for Anti-Aging Interventions.
TL;DR: Cutting-edge research on aging biomarkers at the molecular, cellular, and organismal levels are reviewed, thus shedding light on the relations between aging and telomeres, longevity proteins, a senescence-associated secretory phenotype, the gut microbiota and metabolic patterns.
Journal ArticleDOI
Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease
TL;DR: It is proposed that citrate may be an active component of the senescence-associated secretory phenotype and via its intake through the diet may even contribute to the cause of age-related disease.
Journal ArticleDOI
Senescent cells in the development of cardiometabolic disease.
Andrea C. Postmus,Ines Sturmlechner,Johan W. Jonker,Jan M. van Deursen,Bart van de Sluis,Janine K. Kruit +5 more
TL;DR: The metabolic consequences of senescent cell accumulation in various tissues are now unravelling and point to new therapeutic opportunities for the treatment of cardiometabolic diseases.
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