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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A large-scale CRISPR screen and identification of essential genes in cellular senescence bypass.
Xuehui Liu,Xuehui Liu,Lei Wei,Qiongye Dong,Qiongye Dong,Liyang Liu,Michael Q. Zhang,Michael Q. Zhang,Zhen Xie,Xiaowo Wang +9 more
TL;DR: Interestingly, in the bypass cells, the expression of SASP genes was maintained or elevated with CHEK2, HAS1, or MDK deficiency; but neutralized with MTOR, CRISPLD2, or MORF4L1 deficiency.
Journal ArticleDOI
Nrg1/ErbB signaling‐mediated regulation of fibrosis after myocardial infarction
TL;DR: The molecular mechanism underlying the regulation of fibrotic tissue formation in the infarcted myocardium was shown to be attenuation of apoptosis and senescence of cardiac fibroblasts by the activation of Nrg1/ErbB/PI3K/Akt signaling.
Journal ArticleDOI
Pulmonary Artery Smooth Muscle Cell Senescence Promotes the Proliferation of PASMCs by Paracrine IL-6 in Hypoxia-Induced Pulmonary Hypertension
Ai-Ping Wang,Fang Yang,Ying Tian,Jian-Hui Su,Qing Gu,Wei Chen,Shao-Xin Gong,Xiao-Feng Ma,Xu-Ping Qin,Zhi-Sheng Jiang +9 more
TL;DR: Wang et al. as discussed by the authors demonstrated that PASMC senescence played an essential role in hypoxia-induced pulmonary arterial hypertension (PH) proliferation via increasing the expression of paracrine IL-6 (senescence-associated secretory phenotype).
Dissertation
Characterization of epigenetic and transcriptional changes in aging and Alzheimer’s disease
TL;DR: It is found that dietary and/or genetic folate metabolism disruption leads to alterations on short-term recognition memory, brain gene expression of APP-processing enzymes, neurotrophic factors, histone-acetylation and DNA methylation regulatory enzymes, and their role in orchestrating physical exercise and folate deficiency effects on brain health.
Posted ContentDOI
Loss of SATB1 Induces a p21 Dependent Cellular Senescence Phenotype in Dopaminergic Neurons
Markus Riessland,Benjamin Kolisnyk,Tae Wan Kim,Jia Cheng,Jason Ni,Jordan A. Pearson,Emily J. Park,Kevin Dam,Devrim Acehan,Lavoisier Ramos-Espiritu,Wei Wang,Jack Zhang,Jae-Won Shim,Gabriele Ciceri,Lars Brichta,Lorenz Studer,Paul Greengard +16 more
TL;DR: It is reported that SATB1 prevents cellular senescence in post-mitotic dopaminergic neurons and directly represses expression of the pro-senescence factor, p21, in dopamine neurons in vitro and in vivo.
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