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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Tau Oligomer Induced HMGB1 Release Contributes to Cellular Senescence and Neuropathology Linked to Alzheimer's Disease and Frontotemporal Dementia
Sagar Gaikwad,Nicha Puangmalai,Alice Bittar,Mauro Montalbano,Stephanie Garcia,Salome McAllen,Nemil Bhatt,Urmi Sengupta,Rakez Kayed +8 more
TL;DR: Despite the developed tauopathy in 12-month-old hTau mice, EP+GA treatment significantly decreased TauO and senescent cell loads in the brain, reduced neuroinflammation, and thus ameliorated cognitive functions.
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Molecular mechanisms of ageing and related diseases
TL;DR: The molecular mechanisms underlying the ageing of various cell types, the newly described developmental and programmed replicative senescence and the critical roles of cellular organelles and effectors in Parkinson's disease, diabetes, hypertension and dyskeratosis congenita are provided.
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Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence
Ha-Neui Kim,Jinhu Xiong,Ryan S. MacLeod,Srividhya Iyer,Yuko Fujiwara,Keisha M. Cawley,Li Han,Yonghan He,Jeff D. Thostenson,Elisabeth Ferreira,Robert L. Jilka,Daohong Zhou,Maria Almeida,Charles A. O'Brien +13 more
TL;DR: The results demonstrate the requirement of osteocyte-derived RANKL for age-associated cortical bone loss and suggest that increased Tnfsf11 expression with age results from accumulation of senescent cells in cortical bone.
Journal ArticleDOI
Pleiotropic Effects of Tocotrienols and Quercetin on Cellular Senescence: Introducing the Perspective of Senolytic Effects of Phytochemicals.
Marco Malavolta,Elisa Pierpaoli,Robertina Giacconi,Laura Costarelli,Francesco Piacenza,Andrea Basso,Maurizio Cardelli,Mauro Provinciali +7 more
TL;DR: The rejuvenating effects of T3s and QUE on pre- senescent and senescent primary cells might be the net results of a senolytic activity on senescent cells and a selective survival of a sub-population of non-senescent cells in the culture.
Journal ArticleDOI
Overcoming the senescence-associated secretory phenotype (SASP): a complex mechanism of resistance in the treatment of cancer.
Cecilia R. Chambers,Cecilia R. Chambers,Shona Ritchie,Shona Ritchie,Brooke A. Pereira,Brooke A. Pereira,Paul Timpson,Paul Timpson +7 more
TL;DR: This review will focus on recent evidence regarding therapy‐induced senescence (TIS) from anticancer agents, including chemotherapy, radiation, immunotherapy, and targeted therapies, and how each therapy can trigger the SASP, which in turn influences treatment efficacy.
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