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https://www.readbyqxmd.com/read/29146100/emerging-role-of-extracellular-vesicles-as-a-senescence-associated-secretory-phenotype-insights-into-the-pathophysiology-of-lung-diseases
#1
REVIEW
Tsukasa Kadota, Yu Fujita, Yusuke Yoshioka, Jun Araya, Kazuyoshi Kuwano, Takahiro Ochiya
Aging is a major risk factor for the development of chronic lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. A main aspect of aging is the impaired function of maintaining homeostasis in the organs and body, which is associated with cellular senescence. Cellular senescence is recognized as the state of irreversible cell cycle arrest in response to a variety of cellular stresses. Senescent cells are not simply cell cycle-arrested cells; they also affect bystander cells through the secretion of bioactive molecules, termed the senescence-associated secretory phenotype (SASP)...
November 13, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29143360/identification-of-a-pyridine-derivative-inducing-senescence-in-ovarian-cancer-cell-lines-via-p21-activation
#2
Dongsheng Shang, Yanfang Wu, Ya Ding, Ziwen Lu, Yanting Shen, Feifei Zhu, Hanqing Liu, Chunyin Zhu, Zhigang Tu
Cellular senescence is a state of irreversible cell growth arrest. Increasing evidence suggests that cellular senescence contribute to tumor suppression in vivo. However, only a few anti-cancer drugs have been discovered to induce cellular senescence. Searching for new compounds which can inhibit cancer cell growth by inducing senescence is becoming one of the most attractive research fields. To test the effects of candidate compounds on cancer cell growth, cell proliferation assays, senescence associated β-galactosidase (SA-β-gal) staining, and flow cytometry assay were performed...
November 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29138277/coupling-shrna-screens-with-single-cell-rna-seq-identifies-a-dual-role-for-mtor-in-reprogramming-induced-senescence
#3
Marieke Aarts, Athena Georgilis, Meryam Beniazza, Patrizia Beolchi, Ana Banito, Thomas Carroll, Marizela Kulisic, Daniel F Kaemena, Gopuraja Dharmalingam, Nadine Martin, Wolf Reik, Johannes Zuber, Keisuke Kaji, Tamir Chandra, Jesús Gil
Expression of the transcription factors OCT4, SOX2, KLF4, and cMYC (OSKM) reprograms somatic cells into induced pluripotent stem cells (iPSCs). Reprogramming is a slow and inefficient process, suggesting the presence of safeguarding mechanisms that counteract cell fate conversion. One such mechanism is senescence. To identify modulators of reprogramming-induced senescence, we performed a genome-wide shRNA screen in primary human fibroblasts expressing OSKM. In the screen, we identified novel mediators of OSKM-induced senescence and validated previously implicated genes such as CDKN1A We developed an innovative approach that integrates single-cell RNA sequencing (scRNA-seq) with the shRNA screen to investigate the mechanism of action of the identified candidates...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29133134/sensing-the-breaks-cytosolic-chromatin-in-senescence-and-cancer
#4
Raffaella Di Micco
Cellular senescence constitutes a stable growth arrest characterized by DNA damage response (DDR) activation and by the senescence-associated secretory phenotype (SASP). SASP, through its paracrine effects, stimulates the immune system for senescence eradication. Similarly, chemotherapy-treated cancers activate an interferon-mediated response to induce anti-tumor immunity. Recent studies now uncover a new role for the innate DNA sensing pathway in the recognition of cytosolic chromatin in senescence and cancer...
November 10, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29089421/genetic-interrogation-of-replicative-senescence-uncovers-a-dual-role-for-usp28-in-coordinating-the-p53-and-gata4-branches-of-the-senescence-program
#5
Anna E Mazzucco, Agata Smogorzewska, Chanhee Kang, Ji Luo, Michael R Schlabach, Qikai Xu, Rupesh Patel, Stephen J Elledge
Senescence is a terminal differentiation program that halts the growth of damaged cells and must be circumvented for cancer to arise. Here we describe a panel of genetic screens to identify genes required for replicative senescence. We uncover a role in senescence for the potent tumor suppressor and ATM substrate USP28. USP28 controls activation of both the TP53 branch and the GATA4/NFkB branch that controls the senescence-associated secretory phenotype (SASP). These results suggest a role for ubiquitination in senescence and imply a common node downstream from ATM that links the TP53 and GATA4 branches of the senescence response...
October 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/29084133/modulation-of-the-senescence-associated-inflammatory-phenotype-in-human-fibroblasts-by-olive-phenols
#6
Beatrice Menicacci, Caterina Cipriani, Francesca Margheri, Alessandra Mocali, Lisa Giovannelli
Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the "senescence-associated-secretory-phenotype" (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4-6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers...
October 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29074538/tgf-%C3%AE-promotes-genomic-instability-after-loss-of-runx3
#7
Vaidehi Krishnan, Yu Lin Chong, Tuan Zea Tan, Madhura D Kulkarni, Muhammad Bakhait Bin Rahmat, Lavina Sierra Tay, Doorgesh S Jokhun, Amudha Ganesan, Linda Shyue Huey Chuang, Dominic Chih-Cheng Voon, Shivashankar Gv, Jean Paul Thiery, Yoshiaki Ito
Studies of genomic instability have historically focused on intrinsic mechanisms rather than extrinsic mechanisms based on the tumor microenvironment (TME). TGF-β is the most abundantly secreted cytokine in the TME where it imparts various aggressive characteristics including invasive migration, drug resistance and epithelial-to-mesenchymal transition (EMT). Here we show that TGF-β also promotes genomic instability in the form of DNA double strand breaks (DSB) in cancer cells which lack the tumor suppressor gene RUNX3...
October 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29052866/runx-mediated-growth-arrest-and-senescence-are-attenuated-by-diverse-mechanisms-in-cells-expressing-runx1-fusion-oncoproteins
#8
Gail Anderson, Nancy Mackay, Kathryn Gilroy, Jodie Hay, Gillian Borland, Alma McDonald, Margaret Bell, Siti Ayuni Hassanudin, Ewan Cameron, James C Neil, Anna Kilbey
RUNX gene over-expression inhibits growth of primary cells but transforms cells with tumor suppressor defects, consistent with reported associations with tumor progression. In contrast, chromosomal translocations involving RUNX1 are detectable in utero, suggesting an initiating role in leukemias. How do cells expressing RUNX1 fusion oncoproteins evade RUNX-mediated growth suppression? Previous studies showed that the TEL-RUNX1 fusion from t(12;21) B-ALLs is unable to induce senescence-like growth arrest (SLGA) in primary fibroblasts while potent activity is displayed by the RUNX1-ETO fusion found in t(8;21) AMLs...
October 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29044508/differentially-regulated-gene-expression-in-quiescence-vs-senescence-and-identification-of-arid5a-as-a-quiescence-associated-marker
#9
Tarique Anwar, Bijoya Sen, Savera Aggarwal, Rhisita Nath, Ajay Katoch, Mohamed Aiyaz, Nirupma Trehanpati, Sanjeev Khosla, Gayatri Ramakrishna
In multicellular organisms majority of the cells remain in a non-dividing states of either fully differentiated or quiescence (reversible) or senescence (irreversible) conditions. In the present study, gene expression signatures unique to quiescence and senescence were identified using microarray in osteosarcoma cell line, U2OS. Besides, it was also noted that certain genes and pathways like NOD pathway was shared by both the growth arrest conditions. A major highlight of the present study was increased expression of number of chemokines and cytokines in both quiescence and senescence...
October 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29041897/small-molecule-modulation-of-splicing-factor-expression-is-associated-with-rescue-from-cellular-senescence
#10
Eva Latorre, Vishal C Birar, Angela N Sheerin, J Charles C Jeynes, Amy Hooper, Helen R Dawe, David Melzer, Lynne S Cox, Richard G A Faragher, Elizabeth L Ostler, Lorna W Harries
BACKGROUND: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence...
October 17, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29024417/human-cd8-emra-t-cells-display-a-senescence-associated-secretory-phenotype-regulated-by-p38-mapk
#11
Lauren A Callender, Elizabeth C Carroll, Robert W J Beal, Emma S Chambers, Sussan Nourshargh, Arne N Akbar, Sian M Henson
Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP). We show here that primary human senescent CD8(+) T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age-associated inflammation. We found the CD8(+) CD45RA(+) CD27(-) EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/28993289/sirt1-and-parp1-as-epigenome-safeguards-and-micrornas-as-sasp-associated-signals-in-cellular-senescence-and-aging
#12
REVIEW
Seyedhossein Hekmatimoghaddam, Ali Dehghani Firoozabadi, Mohamad Reza Zare-Khormizi, Fatemeh Pourrajab
Cellular senescence (CS) is underlying mechanism of organism aging and is closely interconnected with age-related diseases (ARDs). Thus, any attempt that influences CS, may be undertaken to reverse or inhibit senescence, whereby could prolong healthy life span. Until now, two main proposes are epigenetic and genetic modifications of cell fate. The first one concerns rejuvenation through effective reprogramming in cells undergoing senescence, or derived from very old or progeroid patients, by which is effective in vitro in induced pluripotent stem cells (iPSCs)...
November 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28991260/protein-and-chemotherapy-profiling-of-extracellular-vesicles-harvested-from-therapeutic-induced-senescent-triple-negative-breast-cancer-cells
#13
E L Kavanagh, S Lindsay, M Halasz, L C Gubbins, K Weiner-Gorzel, M H Z Guang, A McGoldrick, E Collins, M Henry, A Blanco-Fernández, P O' Gorman, P Fitzpatrick, M J Higgins, P Dowling, A McCann
Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy...
October 9, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28987319/mitochondria-telomeres-and-cell-senescence-implications-for-lung-ageing-and-disease
#14
REVIEW
Jodie Birch, Peter J Barnes, Joao F Passos
Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP)...
October 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28969091/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#15
REVIEW
Wen-Juan Wang, Guang-Yan Cai, Xiang-Mei Chen
Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936203/modulation-of-gut-microbiome-composition-and-function-in-experimental-colitis-treated-with-sulfasalazine
#16
Haihui Zheng, Mingyi Chen, Yuan Li, Yuanyuan Wang, Lin Wei, Ziqiong Liao, Mengxia Wang, Fangli Ma, Qiongfeng Liao, Zhiyong Xie
Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28921472/telomere-damage-response-and-low-grade-inflammation
#17
Lihui Wang, Xianhua Yu, Jun-Ping Liu
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28916310/dietary-restriction-delays-the-secretion-of-senescence-associated-secretory-phenotype-by-reducing-dna-damage-response-in-the-process-of-renal-aging
#18
Wenjuan Wang, Guangyan Cai, Xiangmei Chen
Dietary restriction (DR) has multiple and essential effects in protecting against DNA damage in model organisms. Persistent DNA damage plays a central role in the process of aging. Senescence-associated secretory phenotype (SASP), as a product of cellular aging, can accelerate the process of cellular senescence as a feedback. In this study, we directly observed whether a DR of 30% for 6months in aged rats could retard SASP by delaying the progression of DNA damage and also found the specific mechanism. The results revealed that a 30% DR could significantly improve renal pathology and some metabolic characteristics...
September 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28903474/nitric-oxide-heat-shock-protein-axis-in-menopausal-hot-flushes-neglected-metabolic-issues-of-chronic-inflammatory-diseases-associated-with-deranged-heat-shock-response
#19
Antônio Azambuja Miragem, Paulo Ivo Homem de Bittencourt
BACKGROUND: Although some unequivocal underlying mechanisms of menopausal hot flushes have been demonstrated in animal models, the paucity of similar approaches in humans impedes further mechanistic outcomes. Human studies might show some as yet unexpected physiological mechanisms of metabolic adaptation that permeate the phase of decreased oestrogen levels in both symptomatic and asymptomatic women. This is particularly relevant because both the severity and time span of hot flushes are associated with increased risk of chronic inflammatory disease...
September 1, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28894697/the-potential-role-of-senescence-as-a-modulator-of-platelets-and-tumorigenesis
#20
Claudio A Valenzuela, Ricardo Quintanilla, Rodrigo Moore-Carrasco, Nelson E Brown
In addition to thrombus formation, alterations in platelet function are frequently observed in cancer patients. Importantly, both thrombus and tumor formation are influenced by age, although the mechanisms through which physiological aging modulates these processes remain poorly understood. In this context, the potential effects of senescent cells on platelet function represent pathophysiological mechanisms that deserve further exploration. Cellular senescence has traditionally been viewed as a barrier to tumorigenesis...
2017: Frontiers in Oncology
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