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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Legumain-deficient macrophages promote senescence of tumor cells by sustaining JAK1/STAT1 activation
Long Shen,Lichun Kang,Dekun Wang,Jing Xun,Chuan'ai Chen,Lingfang Du,Mianzhi Zhang,Junbo Gong,Xue Mi,Shijing Yue,Yuying Zhang,Xiangrong Song,Rong Xiang,Zhujun Zhang,Xiaoyue Tan +14 more
TL;DR: It is shown that deletion of legumain in macrophages activates senescence of tumor cells, highlighting legumains as a potential therapeutic target for tumors.
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Unique signatures of stress-induced senescent human astrocytes
Katrin Simmnacher,Florian Krach,Yanni Schneider,Julian E. Alecu,Lena Mautner,Paulina Klein,Laurent Roybon,Iryna Prots,Wei Xiang,Beate Winner +9 more
TL;DR: It is shown that the PD-linked pesticide rotenone causes astrocyte senescence and the senescent secretome exaggerates roten one-induced neurodegeneration in midbrain neurons differentiated from human induced pluripotent stem cells (hiPSC) of PD patients with alpha-synuclein gene (SNCA) locus duplication.
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Inhibition of cellular communication network factor 1 (CCN1)-driven senescence slows down cartilage inflammaging and osteoarthritis.
Meng Feng,Hang Peng,Ricky Yao,Ricky Yao,Zhifeng Zhang,Zhifeng Zhang,Genwen Mao,Haiquan Yu,Yusheng Qiu +8 more
TL;DR: Tanshinone IIA was able to preserve articular cartilage integrity, suppress CCN1 production, and inhibit SASP factors in human cartilage explants and in aged mice model, and showed new insight into repurposing Tanshin one IIA for slowing down OA advancement in human and mice by inhibiting theCCN1 axis.
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Mitochondria could be a potential key mediator linking the intestinal microbiota to depression
Jiezhong Chen,Luis Vitetta +1 more
TL;DR: It is posited that the intestinal microbiota could affect neuronal mitochondrial function through short‐chain fatty acids such as butyrate and brain inflammatory processes could also be affected through the modulation of gut permeability and blood lipopolysaccharide levels.
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Senescence in osteoarthritis: from mechanism to potential treatment
TL;DR: In this paper , the latent mechanism of senescence in OA and potential therapeutic methods to target osteoarthritis-related chondrocyte-senescence with an emphasis on immunotherapies were discussed.
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