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senescence associated secretory phenotype

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https://www.readbyqxmd.com/read/29693219/reduction-of-premature-aging-markers-after-gastric-bypass-surgery-in-morbidly-obese-patients
#1
P J Hohensinner, C Kaun, B Ebenbauer, M Hackl, S Demyanets, D Richter, M Prager, J Wojta, Gersina Rega-Kaun
BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype...
April 25, 2018: Obesity Surgery
https://www.readbyqxmd.com/read/29691234/drug-induced-senescent-multiple-myeloma-cells-elicit-nk-cell-proliferation-by-direct-or-exosome-mediated-il-15-trans-presentation
#2
Cristiana Borrelli, Biancamaria Ricci, Elisabetta Vulpis, Cinzia Fionda, Maria Rosaria Ricciardi, Maria Teresa Petrucci, Laura Masuelli, Agnese Peri, Marco Cippitelli, Alessandra Zingoni, Angela Santoni, Alessandra Soriani
Treatment of multiple myeloma (MM) cells with sub-lethal doses of genotoxic drugs leads to senescence and results in increased NK cell recognition and effector functions. Herein we demonstrated that doxorubicin- and melphalan-treated senescent cells display increased expression of IL15, a cytokine involved in NK cell activation, proliferation, and maturation. IL15 up-regulation was evident at the mRNA and protein level, both in MM cell lines and malignant plasma cells (PCs) from patients' bone marrow (BM) aspirates...
April 24, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29688903/cellular-senescence-in-the-treatment-of-ovarian-cancer
#3
Zehua Wang, Haiou Liu, Congjian Xu
OBJECTIVE: This review aimed to update the research and development of cellular senescence in the treatment of ovarian cancer. We discussed the current mechanisms of senescence and the major biomarkers of senescence, especially the methods of cellular senescence in the treatment of ovarian cancer. MATERIALS AND METHODS: We collected all relevant studies in PubMed from 1995 to 2017. The search terms included senescence and cancer, senescence and ovarian cancer, senescence-associated secretory phenotype, ovarian cancer and chemotherapy, radiotherapy, or biotherapy...
April 23, 2018: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/29686666/age-and-age-related-diseases-role-of-inflammation-triggers-and-cytokines
#4
REVIEW
Irene Maeve Rea, David S Gibson, Victoria McGilligan, Susan E McNerlan, H Denis Alexander, Owen A Ross
Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29677534/punicalagin-induces-senescent-growth-arrest-in-human-papillary-thyroid-carcinoma-bcpap-cells-via-nf-%C3%AE%C2%BAb-signaling-pathway
#5
Xian Cheng, Xin Yao, Shichen Xu, Jie Pan, Huixin Yu, Jiandong Bao, Haixia Guan, Rongrong Lu, Li Zhang
Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma. Our previous study revealed that punicalagin (PUN), an active component from pomegranate, triggered autophagic cell death and DNA damage response (DDR) in papillary thyroid carcinoma BCPAP cells. But the detailed anti-cancer mechanisms of punicalagin against PTC still remained to be further explored. DDR activation is a proven cause of cellular senescence, which mediates anti-tumor processes under certain circumstances. In this study, we reported that punicalagin treatment generated a senescent phenotype of BCPAP cells characterized as altered morphology, increased cell granularity and senescence-associated β-galactosidase (SA-β-Gal) staining...
April 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29675264/blocking-negative-effects-of-senescence-in-human-skin-fibroblasts-with-a-plant-extract
#6
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, Anaïs Tromeur, Lionel Weinberg, Juan Carlos Higareda Almaraz, Marcel Scheideler, Marion Rietveld, Abdoel El Ghalbzouri, Erwin Tschachler, Florian Gruber, Johannes Grillari
There is increasing evidence that senescent cells are a driving force behind many age-related pathologies and that their selective elimination increases the life- and healthspan of mice. Senescent cells negatively affect their surrounding tissue by losing their cell specific functionality and by secreting a pro-tumorigenic and pro-inflammatory mixture of growth hormones, chemokines, cytokines and proteases, termed the senescence-associated secretory phenotype (SASP). Here we identified an extract from the plant Solidago virgaurea subsp...
2018: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29675106/overexpression-of-klotho-inhibits-helf-fibroblasts-sasp-related-protumoral-effects-on-non-small-cell-lung-cancer-cells
#7
Bo Chen, Yan Liang, Liben Chen, Yunyan Wei, Yue Li, Weihong Zhao, Jianqing Wu
Lung cancer (LC) is the most common cause of death from cancer worldwide, and it is also a closely aging-related disease. Klotho, a new anti-aging gene, has been proven to play a critical role in regulating aging and the development of age-related diseases including LC. However, whether Klotho is a key link between aging and LC is still unknown. Here we report that Klotho can indirectly inhibit LC growth and development through regulating senescence-associated secretory phenotype (SASP). We found that senescent lung fibroblasts (SLF) can promote production of IL-6 and IL-8, which can be effectively inhibited by overexpressing Klotho...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29670296/paracrine-roles-of-cellular-senescence-in-promoting-tumourigenesis
#8
REVIEW
Jose Mario Gonzalez-Meljem, John Richard Apps, Helen Christina Fraser, Juan Pedro Martinez-Barbera
Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling phenotypes. Although senescence has historically been considered a protective mechanism against tumourigenesis, the activities of senescent cells are increasingly being associated with age-related diseases, including cancer. An important feature of senescent cells is the secretion of a vast array of pro-inflammatory cytokines, chemokines, and growth factors collectively known as the senescence-associated secretory phenotype (SASP)...
April 19, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29608139/senescent-cells-and-osteoarthritis-a-painful-connection
#9
Ok Hee Jeon, Nathaniel David, Judith Campisi, Jennifer H Elisseeff
Senescent cells (SnCs) are associated with age-related pathologies. Osteoarthritis is a chronic disease characterized by pain, loss of cartilage, and joint inflammation, and its incidence increases with age. For years, the presence of SnCs in cartilage isolated from patients undergoing total knee artificial implants has been noted, but these cells' relevance to disease was unclear. In this Review, we summarize current knowledge of SnCs in the multiple tissues that constitute the articular joint. New evidence for the causative role of SnCs in the development of posttraumatic and age-related arthritis is reviewed along with the therapeutic benefit of SnC clearance...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29608137/mechanisms-and-functions-of-cellular-senescence
#10
Nicolás Herranz, Jesús Gil
Cellular senescence is a highly stable cell cycle arrest that is elicited in response to different stresses. By imposing a growth arrest, senescence limits the replication of old or damaged cells. Besides exiting the cell cycle, senescent cells undergo many other phenotypic alterations such as metabolic reprogramming, chromatin rearrangement, or autophagy modulation. In addition, senescent cells produce and secrete a complex combination of factors, collectively referred as the senescence-associated secretory phenotype, that mediate most of their non-cell-autonomous effects...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29593264/downregulation-of-cytoplasmic-dnases-is-implicated-in-cytoplasmic-dna-accumulation-and-sasp-in-senescent-cells
#11
Akiko Takahashi, Tze Mun Loo, Ryo Okada, Fumitaka Kamachi, Yoshihiro Watanabe, Masahiro Wakita, Sugiko Watanabe, Shimpei Kawamoto, Kenichi Miyata, Glen N Barber, Naoko Ohtani, Eiji Hara
Accumulating evidence indicates that the senescence-associated secretory phenotype (SASP) contributes to many aspects of physiology and disease. Thus, controlling the SASP will have tremendous impacts on our health. However, our understanding of SASP regulation is far from complete. Here, we show that cytoplasmic accumulation of nuclear DNA plays key roles in the onset of SASP. Although both DNase2 and TREX1 rapidly remove the cytoplasmic DNA fragments emanating from the nucleus in pre-senescent cells, the expression of these DNases is downregulated in senescent cells, resulting in the cytoplasmic accumulation of nuclear DNA...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29590617/regulation-of-cellular-senescence-by-polycomb-chromatin-modifiers-through-distinct-dna-damage-and-histone-methylation-dependent-pathways
#12
Takahiro Ito, Yee Voan Teo, Shane A Evans, Nicola Neretti, John M Sedivy
Polycomb group (PcG) factors maintain facultative heterochromatin and mediate many important developmental and differentiation processes. EZH2, a PcG histone H3 lysine-27 methyltransferase, is repressed in senescent cells. We show here that downregulation of EZH2 promotes senescence through two distinct mechanisms. First, depletion of EZH2 in proliferating cells rapidly initiates a DNA damage response prior to a reduction in the levels of H3K27me3 marks. Second, the eventual loss of H3K27me3 induces p16 (CDKN2A) gene expression independent of DNA damage and potently activates genes of the senescence-associated secretory phenotype (SASP)...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29577907/possible-role-of-ginsenoside-rb1-in-skin-wound-healing-via-regulating-senescent-skin-dermal-fibroblast
#13
Jingang Hou, Sunchang Kim
Cellular senescence suppresses cancer by inducing irreversible cell growth arrest. Nevertheless, senescent cells is proposed as causal link with aging and aging-related pathologies. The physiological beneficial functions of senescent cells are still of paucity. Here we show that senescent human dermal fibroblast accelerates keratinocytes scratch wound healing and stimulates differentiation of fibroblast. Using oxidative stress (100 μM H2 O2 exposure for 1 h) induction, we successfully triggered fibroblast senescence and developed senescence associated secretory phenotype (SASP)...
March 22, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29550586/unraveling-the-interplay-between-senescent-dermal-fibroblasts-and-cutaneous-squamous-cell-carcinoma-cell-lines-at-different-stages-of-tumorigenesis
#14
Marie Toutfaire, Elise Dumortier, Antoine Fattaccioli, Martine Van Steenbrugge, Charlotte M Proby, Florence Debacq-Chainiaux
Cutaneous Squamous Cell Carcinoma (cSCC) is the second most common type of non-melanoma skin cancer in white-skinned populations. cSCC is associated with sun exposure and aging, which is concomitant with an accumulation of senescent cells in the skin. The involvement of senescent cells in carcinogenesis has been highlighted in several cancer types and an interaction between cSCC cells and senescent cells is proposed, but still little explored. Tumor-associated effects are mostly attributed to the senescence-associated secretory phenotype (SASP)...
March 14, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29549053/senescent-human-hematopoietic-progenitors-show-elevated-expression-of-transposable-elements-and-inflammatory-genes
#15
Stephen Capone, Kwasi M Connor, Anthony Colombo, Xin Li, Tim J Triche, Giridharan Ramsingh
Genomic transposable elements (TEs) constitute majority of the genome. Expression of TEs is known to activate the double-stranded RNA recognition pathway ("viral mimicry") leading to the activation of interferon-stimulated genes, inflammation and immune mediated cell death. We recently showed that the expression of TEs is suppressed along with immune pathways in leukemic stem cells (LSC) in acute myeloid leukemia, suggesting a potential mechanism for immune escape of LSC. This indicated that during oncogenesis, where there is escape from senescence, expression of TEs is suppressed...
March 13, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29527222/age-and-tissue-specific-expression-of-senescence-biomarkers-in-mice
#16
Adam D Hudgins, Cagdas Tazearslan, Archana Tare, Yizhou Zhu, Derek Huffman, Yousin Suh
Cellular senescence is a state of irreversible cellular growth arrest accompanied by distinct changes in gene expression and the acquisition of a complex proinflammatory secretory profile termed the senescence-associated secretory phenotype (SASP). Senescent cells accumulate in aged tissues and contribute to age-related disease in mice. Increasing evidence that selective removal of senescent cells can ameliorate diseases of late life and extend lifespan in mice has given rise to the development of senolytics that target senescent cells as anti-aging therapeutics...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29470431/articular-cartilage-aging-potential-regenerative-capacities-of-cell-manipulation-and-stem-cell-therapy
#17
REVIEW
Magdalena Krajewska-Włodarczyk, Agnieszka Owczarczyk-Saczonek, Waldemar Placek, Adam Osowski, Joanna Wojtkiewicz
Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products...
February 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29463096/inhibition-of-radiation-induced-ccl2-signaling-protects-lungs-from-vascular-dysfunction-and-endothelial-cell-loss
#18
Alina Wiesemann, Julia Ketteler, Alexis Slama, Florian Wirsdörfer, Thomas Hager, Katharina Roeck, Daniel Engel, Jens Fischer, Clemens Aigner, Verena Jendrossek, Diana Klein
AIMS: Radiation-induced normal tissue toxicity often precludes the application of curative radiation doses. Here we investigated the therapeutic potential of Ccl2 signaling inhibition to protect normal lung tissue from radiotherapy (RT)-induced injury. RESULTS: RT-induced vascular dysfunction and associated adverse effects can be efficiently antagonized by inhibition of Ccl2 signaling using either the selective Ccl2 inhibitor bindarit (BIN) or mice deficient for the main Ccl2 receptor CCR2 (KO)...
February 20, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29457783/cellular-senescence-in-brain-aging-and-neurodegenerative-diseases-evidence-and-perspectives
#19
Darren J Baker, Ronald C Petersen
Along with a general decline in overall health, most chronic degenerative human diseases are inherently associated with increasing age. Age-associated cognitive impairments and neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases, are potentially debilitating conditions that lack viable options for treatment, resulting in a tremendous economic and societal cost. Most high-profile clinical trials for neurodegenerative diseases have led to inefficacious results, suggesting that novel approaches to treating these pathologies are needed...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29449647/the-pro-inflammatory-phenotype-of-the-human-non-classical-monocyte-subset-is-attributed-to-senescence
#20
Siew-Min Ong, Eva Hadadi, Truong-Minh Dang, Wei-Hseun Yeap, Crystal Tze-Ying Tan, Tze-Pin Ng, Anis Larbi, Siew-Cheng Wong
Human primary monocytes comprise a heterogeneous population that can be classified into three subsets based on CD14 and CD16 expression: classical (CD14 high /CD16 - ), intermediate (CD14 high /CD16 + ), and non-classical (CD14 low /CD16 + ). The non-classical monocytes are the most pro-inflammatory in response to TLR stimulation in vitro, yet they express a remarkably high basal level of miR-146a, a microRNA known to negatively regulate the TLR pathway. This concurrence of a pro-inflammatory status and a high miR-146a level has been associated with cellular senescence in other cell types...
February 15, 2018: Cell Death & Disease
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