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
Identification of a novel senomorphic agent, avenanthramide C, via the suppression of the senescence-associated secretory phenotype.
Jae Sung Lim,Da Young Lee,Hyung-Seok Kim,Sang Chul Park,Joon Tae Park,Hyeon Sik Kim,Won Keun Oh,Kyung A Cho +7 more
TL;DR: An avenanthramice C extracted from oat is reported as a new SASP modulator that led to a significant reduction in the levels of markers of senescent cells, with no toxicity observed and the mechanism underlying SASP inhibition by Avn C was investigated.
Journal ArticleDOI
Dissecting primary and secondary senescence to enable new senotherapeutic strategies.
TL;DR: In this paper, the authors proposed to use the senescence-associated secretory phenotype (SASP) to detect the presence of a small number of senescent cells.
Journal ArticleDOI
Cellular senescence occurred widespread to multiple selective sites in the fetal tissues and organs of mice
TL;DR: The present findings suggest that cellular senescence represents an essential mechanism at multiple sites including the fetal bone forming zones and placenta during mammalian embryonic development, playing potential roles in the full embryonic development of tissue growth and organ formation.
Journal ArticleDOI
Porphyromonas gingivalis Provokes Exosome Secretion and Paracrine Immune Senescence in Bystander Dendritic Cells
Ranya Elsayed,Mahmoud Elashiry,Yutao Liu,Ahmed El-Awady,Mark W. Hamrick,Christopher W. Cutler +5 more
TL;DR: In this article, the authors examined whether immune cells typical of those at the oral mucosa-microbe interface, are vulnerable to cellular senescence and the role of dysbiotic oral pathogen Porphyromonas gingivalis.
Journal ArticleDOI
Recent advances and future avenues in understanding the role of adipose tissue cross talk in mediating skeletal muscle mass and function with ageing.
TL;DR: The role of extracellular vesicles in mediating inter-tissue cross talk via lncRNAs and miRNAs in the context of sarcopenia, ageing, and obesity is discussed in this paper.
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.