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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
The complex entanglement of Hippo-Yap/Taz signaling in tumor immunity
TL;DR: It is clear that Hippo signaling functions as a key bridge connecting tumor cells with both the adaptive and innate immune systems, and all future therapeutic development against the Hippo-Yap/Taz pathway should take into account their multi-faceted roles in regulating tumor immunity in addition to their growth-regulatory functions.
Posted ContentDOI
A Multidimensional Systems Biology Analysis of Cellular Senescence in Ageing and Disease
Roberto A. Avelar,Javier Gómez Ortega,Javier Gómez Ortega,Robi Tacutu,Robi Tacutu,Eleanor J. Tyler,Dominic Bennett,Paolo Binetti,Arie Budovsky,Kasit Chatsirisupachai,Emily Johnson,Alex Murray,Samuel Shields,Daniela Tejada-Martinez,Daniela Tejada-Martinez,Daniel Thornton,Vadim E. Fraifeld,Cleo L. Bishop,João Pedro de Magalhães +18 more
TL;DR: This work created CellAge, a manually curated database of 279 human genes associated with cellular senescence, and performed various integrative and functional analyses that observed that genes promoting cellsenescence tend to be overexpressed with age in human tissues and are also significantly overrepresented in anti-longevity and tumour-suppressor gene databases.
Journal ArticleDOI
Immunosenescence: the Role of Aging in the Predisposition to Neuro-Infectious Complications Arising from the Treatment of Multiple Sclerosis
TL;DR: Immunosenescence-associated changes may be additive or synergistic with the effects produced by immunomodulatory and immunosuppressive medications and Clinicians should exercise a high level of vigilance in monitoring the risk of infections in older patients on these treatments.
Journal ArticleDOI
Embryonic Stem Cell-Derived mmu-miR-291a-3p Inhibits Cellular Senescence in Human Dermal Fibroblasts Through the TGF-β Receptor 2 Pathway.
Yun-Ui Bae,Youlim Son,Chang-Hyun Kim,Kwang Seok Kim,Se Hee Hyun,Hyun Goo Woo,Byul A. Jee,Jun-Hyuk Choi,Hoon Ki Sung,Hyung-Chul Choi,So-Young Park,Ju-Hyun Bae,Kyung-Oh Doh,Jae-Ryong Kim +13 more
TL;DR: The results indicate that the ESC-derived mmu-miR-291a-3p is a novel candidate agent that can be utilized for cell-free therapeutic intervention against aging and aging-related diseases.
Journal ArticleDOI
Blocking negative effects of senescence in human skin fibroblasts with a plant extract
Ingo Lämmermann,Lucia Terlecki-Zaniewicz,Regina Weinmüllner,Markus Schosserer,Hanna Dellago,André Dargen de Matos Branco,Dominik Autheried,Benjamin Sevcnikar,Lisa Kleissl,Irina Berlin,Frédérique Morizot,Francois Lejeune,Nicola Fuzzati,Sandra Forestier,Alix Toribio,Anais Tromeur,Lionel Weinberg,Juan Carlos Higareda Almaraz,Marcel Scheideler,Marion Rietveld,Abdoel El Ghalbzouri,Erwin Tschachler,Florian Gruber,Johannes Grillari +23 more
TL;DR: An extract from the plant Solidago virgaurea subsp.
References
More filters
Journal ArticleDOI
The serial cultivation of human diploid cell strains.
Leonard Hayflick,P.S. Moorhead +1 more
TL;DR: A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.
Journal ArticleDOI
The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI
Cellular senescence: when bad things happen to good cells
TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
Journal ArticleDOI
TGFβ in Cancer
TL;DR: The mechanistic basis and clinical relevance of TGFbeta's role in cancer is becoming increasingly clear, paving the way for a better understanding of the complexity and therapeutic potential of this pathway.
Journal ArticleDOI
Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor
Jean-Philippe Coppe,Christopher K. Patil,Francis Rodier,Francis Rodier,Yun-Yu Sun,Denise P. Muñoz,Denise P. Muñoz,Joshua Goldstein,Peter S. Nelson,Pierre-Yves Desprez,Pierre-Yves Desprez,Judith Campisi,Judith Campisi +12 more
TL;DR: A cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment is suggested.