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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Vascular smooth muscle cell senescence and age-related diseases: State of the art.
TL;DR: The purpose of this paper was to review the current knowledge regarding VSMC senescence and its relevance to hypertension, atherosclerosis, and diabetes, as well as the potential mechanisms responsible for VSMCsenescence in these age-related diseases.
Journal ArticleDOI
Senescence associated secretory phenotype profile from primary lung mice fibroblasts depends on the senescence induction stimuli
Luis Ángel Maciel-Barón,Sandra Lizbeth Morales-Rosales,A. A. Aquino-Cruz,Francisco Triana-Martínez,Sonia Galván-Arzate,Armando Luna-López,Viridiana Y. González-Puertos,Norma Edith López-Diazguerrero,Claudio Torres,Mina Königsberg +9 more
TL;DR: The results showed important variations in the 62 cytokines analyzed, while SIPS and RS showed an increase in the secretion of most cytokines, and in PIIPS only 13 were incremented, suggesting that the senescence induction pathway might encompass dissimilar responses in adjacent cells and promote different outcomes.
Journal ArticleDOI
Immunology of the ageing kidney.
Yuki Sato,Motoko Yanagita +1 more
TL;DR: How the processes of immunosenescence and inflammageing drive these age-related changes, and their effects on the ageing kidney are discussed.
Journal ArticleDOI
Cortical neurons develop a senescence-like phenotype promoted by dysfunctional autophagy.
Daniel Moreno-Blas,Elisa Gorostieta-Salas,Alexander Pommer-Alba,Gabriel Muciño-Hernández,Cristian Gerónimo-Olvera,Luis Ángel Maciel-Barón,Mina Königsberg,Lourdes Massieu,Susana Castro-Obregón +8 more
TL;DR: This study characterized an in vitro model useful to study the molecular basis of senescence of primary rat cortical cells that recapitulates senescent features described in brain aging and found that in long-term cultures, rat primary cortical neurons displayed features of cellularsenescence before glial cells did.
Journal ArticleDOI
Aging of the cells: Insight into cellular senescence and detection Methods
TL;DR: Different types of cellular senescence including replicativesenescence (RS) which occurs due to telomere shortening and stress induced premature senescences (SIPS), which occurs in response to different types of stress in cells, are discussed.
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