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senescence associated secretory phenotype

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https://www.readbyqxmd.com/read/28330601/mitochondria-in-cell-senescence-is-mitophagy-the-weakest-link
#1
REVIEW
Viktor I Korolchuk, Satomi Miwa, Bernadette Carroll, Thomas von Zglinicki
Cell senescence is increasingly recognized as a major contributor to the loss of health and fitness associated with aging. Senescent cells accumulate dysfunctional mitochondria; oxidative phosphorylation efficiency is decreased and reactive oxygen species production is increased. In this review we will discuss how the turnover of mitochondria (a term referred to as mitophagy) is perturbed in senescence contributing to mitochondrial accumulation and Senescence-Associated Mitochondrial Dysfunction (SAMD). We will further explore the subsequent cellular consequences; in particular SAMD appears to be necessary for at least part of the specific Senescence-Associated Secretory Phenotype (SASP) and may be responsible for tissue-level metabolic dysfunction that is associated with aging and obesity...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#2
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28325222/effects-of-ultra-high-dilutions-of-sodium-butyrate-on-viability-and-gene-expression-in-hek-293-cells
#3
Steven Olsen
BACKGROUND: Several recent studies reported the capability of high diluted homeopathic medicines to modulate gene expression in cell cultures. In line with these studies, we examined whether ultra-high dilutions (30C and 200C) of sodium butyrate (SB) can affect the expression levels of genes involved in acquisition of a senescence-associated secretory phenotype (SASP) in human embryonic kidney (HEK) 293 cells. METHODS: Cell viability was evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay...
February 2017: Homeopathy: the Journal of the Faculty of Homeopathy
https://www.readbyqxmd.com/read/28320873/sav1-loss-induces-senescence-and-stat3-activation-coinciding-with-tubulointerstitial-fibrosis
#4
Janet Y Leung, Harper L Wilson, Kristin J Voltzke, Lindsay A Williams, Hyo Jin Lee, Sara E Wobker, William Y Kim
Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here, we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor, Verteporfin (VP), inhibited activation of genes associated with senescence, SASP and activation of Stat3 as well as impeded the development of fibrosis...
March 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#5
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
https://www.readbyqxmd.com/read/28300842/cd95-ligand-induces-senescence-in-mismatch-repair-deficient-human-colon-cancer-via-chronic-caspase-mediated-induction-of-dna-damage
#6
Danielle A Raats, Nicola Frenkel, Susanne J van Schelven, Inne HMBorel Rinkes, Jamila Laoukili, Onno Kranenburg
CD95 is best known for its ability to induce apoptosis via a well-characterized pathway involving caspase-mediated proteolytic events. However, in apoptosis-resistant cell lines of diverse cancer types stimulation of CD95 primarily has pro-tumorigenic effects that affect many of the hallmarks of cancer. For instance, in colon cancer cells with a mutant KRAS gene CD95 primarily promotes invasion and metastasis. In the current study, we further investigated the context dependency of the consequences of CD95 activation in colon cancer...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299617/methyl-caffeate-and-some-plant-constituents-inhibit-age-related-inflammation-effects-on-senescence-associated-secretory-phenotype-sasp-formation
#7
Hyun Lim, Byung Kyu Park, Sook Young Shin, Yong Soo Kwon, Hyun Pyo Kim
During aging, cells secrete molecules called senescence-associated secretory phenotype (SASP). They constitute chronic low-grade inflammation environment to adjacent cells and tissues. In order to find inhibiting agents of SASP formation, 113 plant constituents were incubated with BJ fibroblasts for 6 days after treatment with bleomycin. Several plant constituents showed considerable inhibition of IL-6 production, a representative SASP marker. These plant constituents included anthraquinones such as aurantio-obtusin, flavonoids including astragalin, iristectorigenin A, iristectorigenin B, linarin, lignans including lariciresinol 9-O-glucoside and eleutheroside E, phenylpropanoids such as caffeic acid and methyl caffeate, steroid (ophiopogonin), and others like centauroside, rhoifolin and scoparone...
March 15, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28286205/ochratoxin-a-induced-premature-senescence-in-human-renal-proximal-tubular-cells
#8
Xuan Yang, Sheng Liu, Chuchu Huang, Haomiao Wang, Yunbo Luo, Wentao Xu, Kunlun Huang
Ochratoxin A (OTA) has many nephrotoxic effects and is a promising compound for the study of nephrotoxicity. Human renal proximal tubular cells (HKC) are an important model for the study of renal reabsorption, renal physiology and pathology. Since the induction of OTA in renal senescence is largely unknown, whether OTA can induce renal senescence, especially at a sublethal dose, and the mechanism of OTA toxicity remain unclear. In our study, a sublethal dose of OTA led to an enhanced senescent phenotype, β-galactosidase staining and senescence associated secretory phenotype (SASP)...
March 9, 2017: Toxicology
https://www.readbyqxmd.com/read/28273461/integrin-beta-3-regulates-cellular-senescence-by-activating-the-tgf-%C3%AE-pathway
#9
Valentina Rapisarda, Michela Borghesan, Veronica Miguela, Vesela Encheva, Ambrosius P Snijders, Amaia Lujambio, Ana O'Loghlen
Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3) is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β) pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS) through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS), independently of its ligand-binding activity...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28273155/tumor-stroma-with-senescence-associated-secretory-phenotype-in-steatohepatitic-hepatocellular-carcinoma
#10
Jee San Lee, Jeong Eun Yoo, Haeryoung Kim, Hyungjin Rhee, Myoung Ju Koh, Ji Hae Nahm, Jin Sub Choi, Kee-Ho Lee, Young Nyun Park
Senescence secretome was recently reported to promote liver cancer in an obese mouse model. Steatohepatitic hepatocellular carcinoma (SH-HCC), a new variant of HCC, has been found in metabolic syndrome patients, and pericellular fibrosis, a characteristic feature of SH-HCC, suggests that alteration of the tumor stroma might play an important role in SH-HCC development. Clinicopathological characteristics and tumor stroma showing senescence and senescence-associated secretory phenotype (SASP) were investigated in 21 SH-HCCs and 34 conventional HCCs (C-HCCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28247536/melatonin-regulates-parp1-to-control-the-senescence-associated-secretory-phenotype-sasp-in-human-fetal-lung-fibroblast-cells
#11
Songtao Yu, Xiaojiao Wang, Peiliang Geng, Xudong Tang, Lisha Xiang, Xin Lu, Jianjun Li, Zhihua Ruan, Jianfang Chen, Ganfeng Xie, Zhe Wang, Juanjuan Ou, Yuan Peng, Xi Luo, Xuan Zhang, Yan Dong, Hongshan Chen, Houjie Liang
Cellular senescence is an important tumor-suppressive mechanism. However, acquisition of a senescence-associated secretory phenotype (SASP) in senescent cells has deleterious effects on the tissue microenvironment and, paradoxically, promotes tumor progression. In a drug screen, we identified melatonin as a novel SASP suppressor in human cells. Strikingly, melatonin blunts global SASP gene expression upon oncogene-induced senescence (OIS). Moreover, poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage, was identified as a new melatonin-dependent regulator of SASP gene induction upon OIS...
March 1, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28245616/the-impacts-of-cellular-senescence-in-elderly-pneumonia-and-in-age-related-lung-diseases-that-increase-the-risk-of-respiratory-infections
#12
REVIEW
Shigehisa Yanagi, Hironobu Tsubouchi, Ayako Miura, Ayako Matsuo, Nobuhiro Matsumoto, Masamitsu Nakazato
Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP)...
February 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28217839/targeting-the-sasp-to-combat-ageing-mitochondria-as-possible-intracellular-allies
#13
Jodie Birch, João F Passos
Anti-senescence therapies, such as drugs that specifically kill senescent cells, to stave off ageing are currently under investigation. While these interventions show promise, their potential pitfalls are discussed herein. We have shown that the mitochondria are essential for development of senescence and many of the associated phenotypes, including the often detrimental senescence-associated secretory phenotype (SASP). Here, we disentangle many ways in which the mitochondria may influence senescence and development of the SASP and focus on possible pathways that could be exploited for future generation of anti-senescence therapies with a clear aim; to specifically eliminate the problematic features of senescent cells, while maintaining their beneficial characteristics...
February 20, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28217805/-induction-of-robust-senescence-associated-secretory-phenotype-in-mouse-nih-3t3-cells-by-mitomycin-c
#14
Wei-Xing Huang, Xiao-Xuan Guo, Zhong-Zhi Peng, Chun-Liang Weng, Chun-Yan Huang, Ben-Yan Shi, Jie Yang, Xiao-Xin Liao, Xiao-Yi Li, Hui-Ling Zheng, Xin-Guang Liu, Xue-Rong Sun
Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present...
February 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#15
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28197538/cancer-cell-cannibalism-and-the-sasp-ripples-in-the-murky-waters-of-tumor-dormancy
#16
Thomas J Bartosh
Relapse in cancer patients following an apparent cure and a prolonged latency period, known as tumor dormancy, remains an unrelenting clinical crisis. Here, I expand on our recent findings that potentially link cancer cell cannibalism of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to the senescence-associated secretory phenotype (SASP) and tumor dormancy.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28185345/the-female-reproduction-and-senescence-nexus
#17
Cielo Mae D Marquez, Joyce A Ibana, Michael C Velarde
Successful pregnancy is regulated by several soluble factors that are differentially expressed throughout gestation. These factors are important to initiate and establish embryo implantation and parturition. Senescent cells, which undergo permanent cell proliferation arrest in response to stress, also produce several secreted factors, referred to as the senescence-associated secretory phenotype (SASP). Here, we review some of the secreted factors found during early and late pregnancy and compare their expression profile with those of the SASP...
February 10, 2017: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/28166834/downregulation-of-mir-130b-301b-cluster-is-mediated-by-aberrant-promoter-methylation-and-impairs-cellular-senescence-in-prostate-cancer
#18
João Ramalho-Carvalho, Inês Graça, Antonio Gomez, Jorge Oliveira, Rui Henrique, Manel Esteller, Carmen Jerónimo
BACKGROUND: Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR), may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa) cells. METHODS: Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip...
February 6, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28165648/the-impact-of-sasp-and-its-potential-as-a-therapeutic-target-for-senescence-associated-diseases
#19
Sugiko Watanabe, Shimpei Kawamoto, Naoko Ohtani, Eiji Hara
'Cellular senescence' is a state in which cells undergo irreversible cell cycle arrest in response to a variety of cellular stresses. Once cells senesce, they are strongly resistant to any mitogens, including oncogenic stimuli. Therefore, cellular senescence has been assumed to be a potent anticancer mechanism. Although irreversible cell-cycle arrest is traditionally considered the major characteristic of senescent cells, recent studies have revealed some additional functions. Most noteworthy is the increased secretion of various secretory proteins, such as inflammatory cytokines, chemokines, growth factors, and matrix metalloproteinases, into the surrounding extracellular fluid...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28143833/the-senescence-associated-secretory-phenotype-induces-cellular-plasticity-and-tissue-regeneration
#20
Birgit Ritschka, Mekayla Storer, Alba Mas, Florian Heinzmann, Mari Carmen Ortells, Jennifer P Morton, Owen J Sansom, Lars Zender, William M Keyes
Senescence is a form of cell cycle arrest induced by stress such as DNA damage and oncogenes. However, while arrested, senescent cells secrete a variety of proteins collectively known as the senescence-associated secretory phenotype (SASP), which can reinforce the arrest and induce senescence in a paracrine manner. However, the SASP has also been shown to favor embryonic development, wound healing, and even tumor growth, suggesting more complex physiological roles than currently understood. Here we uncover timely new functions of the SASP in promoting a proregenerative response through the induction of cell plasticity and stemness...
January 15, 2017: Genes & Development
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