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senescence-associated secretory phenotype

Jia Huo, Zhe Xu, Kazunori Hosoe, Hiroshi Kubo, Hiroki Miyahara, Jian Dai, Masayuki Mori, Jinko Sawashita, Keiichi Higuchi
Oxidative damage in endothelial cells is proposed to play an important role in endothelial dysfunction and atherogenesis. We previously reported that the reduced form of coenzyme Q10 (CoQ10 H2 ) effectively inhibits oxidative stress and decelerates senescence in senescence-accelerated mice. Here, we treated human umbilical vein endothelial cells (HUVECs) with H2 O2 and investigated the protective effect of CoQ10 H2 against senescence, oxidative damage, and reduction in cellular functions. We found that CoQ10 H2 markedly reduced the number of senescence-associated β -galactosidase-positive cells and suppressed the expression of senescence-associated secretory phenotype-associated genes in H2 O2 -treated HUVECs...
2018: Oxidative Medicine and Cellular Longevity
Miriam S Hohmann, David M Habiel, Ana L Coelho, Waldiceu A Verri, Cory M Hogaboam
While cellular senescence may be a protective mechanism in modulating proliferative capacity, fibroblast senescence is now recognized as a key pathogenic mechanism in Idiopathic Pulmonary Fibrosis (IPF). In aged mice, abundance and persistence of apoptosis-resistant senescent fibroblasts play a central role in non-resolving lung fibrosis after bleomycin challenge. Therefore, we investigated whether quercetin can restore the susceptibility of senescent IPF fibroblasts to pro-apoptotic stimuli and mitigate bleomycin-induced pulmonary fibrosis in aged mice...
August 15, 2018: American Journal of Respiratory Cell and Molecular Biology
Qianqian He, Bijin Au, Madhura Kulkarni, Yang Shen, Kah J Lim, Jiamila Maimaiti, Cheng Kit Wong, Monique N H Luijten, Han C Chong, Elaine H Lim, Giulia Rancati, Indrajit Sinha, Zhiyan Fu, Xiaomeng Wang, John E Connolly, Karen C Crasta
Chromosomal instability (CIN), a high rate of chromosome loss or gain, is often associated with poor prognosis and drug resistance in cancers. Aneuploid, including near-polyploid, cells contain an abnormal number of chromosomes and exhibit CIN. The post-mitotic cell fates following generation of different degrees of chromosome mis-segregation and aneuploidy are unclear. Here we used aneuploidy inducers, nocodazole and reversine, to create different levels of aneuploidy. A higher extent of aneuploid and near-polyploid cells in a given population led to senescence...
August 15, 2018: Oncogenesis
Luis Ángel Maciel-Barón, Sandra Lizbeth Morales-Rosales, Alejandro Silva-Palacios, Roxana Haydee Rodríguez-Barrera, Jorge Antonio García-Álvarez, Armando Luna-López, Viviana Isabel Pérez, Claudio Torres, Mina Königsberg
In the central nervous system (CNS), senescent astrocytes have been associated with neurodegeneration. Senescent cells secrete a complex mixture of pro-inflammatory factors, which are collectively called Senescence Associated Secretory Phenotype (SASP). The SASP components can vary depending on the cell type, senescence inducer and time. The SASP has been mainly studied in fibroblasts and epithelial cells, but little is known in the context of the CNS. Here, the SASP profile in senescent astrocytes isolated from Wistar newborn rats induced to senescence by oxidative stress or by proteasome inhibition was analyzed...
August 10, 2018: Biogerontology
Barbara Bellei, Emilia Migliano, Marinella Tedesco, Silvia Caputo, Federica Papaccio, Gianluca Lopez, Mauro Picardo
BACKGROUND: Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secretory factors, demonstrated beneficial effects by reducing tissue damage and stimulation of endogenous repair. However, for therapeutic purposes, the use of secretome derivatives, such as full conditioned media or purified exosomes generated in vitro, may present considerable disadvantages for cell manufacturing, storage, product safety, and their potential as a ready-to-go therapeutic product...
August 9, 2018: Stem Cell Research & Therapy
Minji Bang, Onjeon Ryu, Do Gyeong Kim, Darine Froy Mabunga, Kyu Suk Cho, Yujeong Kim, Seol-Heui Han, Kyoung Ja Kwon, Chan Young Shin
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation...
August 10, 2018: Biomolecules & Therapeutics
Ji Heon Noh, Kyoung Mi Kim, M Laura Idda, Jennifer L Martindale, Xiaoling Yang, Kotb Abdelmohsen, Myriam Gorospe
A prominent phenotype triggered by the loss of mitochondrial homeostasis is cellular senescence, characterized by cessation of growth and a senescence-associated secretory phenotype (SASP). We identified the G-rich RNA sequence-binding factor 1 (GRSF1) as a major mitochondrial protein implicated in this response. GRSF1 levels declined in senescent cells through reduced protein stability, and lowering GRSF1 abundance caused mitochondrial stress leading to elevated production of superoxide, increased DNA damage foci, and diminished cell proliferation...
August 7, 2018: Aging
Beatrice Menicacci, Francesca Margheri, Anna Laurenzana, Anastasia Chillà, Mario Del Rosso, Lisa Giovannelli, Gabriella Fibbi, Alessandra Mocali
Senescent cells are characterized by an increased secretion of inflammatory and growth factors, known as the "senescence-associated secretory phenotype" (SASP), producing a pro-tumoral and pro-angiogenic microenvironment. The present work proposes chronic resveratrol treatment (5 µM for 5 weeks, termed R5) of senescent MRC5 fibroblasts as a mean to mimic and target the angiogenic trait of stromal fibroblast SASP. Senescent fibroblast conditioned medium (CM sen) was effective in enhancing the angiogenic properties of endothelial colony forming cells (ECFC), i...
July 31, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Maria E Laucho-Contreras, Francesca Polverino, Joselyn Rojas-Quintero, Xiaoyun Wang, Caroline A Owen
Low serum CC16 levels are associated with accelerated lung function decline in human population studies, but it is not known whether low serum CC16 levels contribute to lung function decline, or are an epiphenomenon. We tested the hypothesis that unchallenged Cc16-/- mice develop accelerated rates of pulmonary function test abnormalities and pulmonary pathologies over time compared with unchallenged WT mice. Respiratory mechanics, airspace enlargement, and small airway fibrosis were measured in unchallenged wild-type (WT) versus Cc16-/- mice over 6-18 months of age...
August 2018: Physiological Reports
Yu-Yan Lan, Fang-Hsin Chang, Jen-Hao Tsai, Yao Chang
Clinical studies suggest a positive association between malignant progression of nasopharyngeal carcinoma (NPC) and Rta, a transcription factor of Epstein-Barr virus (EBV). However, Rta induces cellular senescence in vitro. To provide an underlying mechanism integrating these clues, we adapted a concept of senescence-associated secretory phenotype (SASP), based on which senescent cells facilitate tumor progression through paracrine. First, Rta-expressing NPC cells themselves show reduced invasiveness but promote invasion of Rta-negative tumor cells through secreted factors...
August 4, 2018: Biochemical and Biophysical Research Communications
Anthony R Colombo, Harold K Elias, Giridharan Ramsingh
Senescent cells constitutively secrete inflammatory cytokines, known as the senescence-associated secretory phenotype (SASP). Previous work has implicated SASP in immune-mediated clearance of senescent cells; however, its regulation remains unknown. Our recent transcriptome profiling study has shown that human senescent human stem and progenitors (s-HSPCs) robustly express genomic transposable elements (TEs) and pathways of inflammation. Furthermore, hypomethylating agents have been previously shown to induce expression of TEs and activate the dsRNA recognition pathway and downstream interferon-stimulated genes, leading to immune mediated cell death...
August 6, 2018: Cell Cycle
Wenqiang Wei, Shaoping Ji
Cellular senescence is the arrest of normal cell division. Oncogenic genes and oxidative stress, which cause genomic DNA damage and generation of reactive oxygen species, lead to cellular senescence. The senescence-associated secretory phenotype is a distinct feature of senescence. Senescence is normally involved in the embryonic development. Senescent cells can communicate with immune cells to invoke an immune response. Senescence emerges during the aging process in several tissues and organs. In fact, increasing evidence shows that cellular senescence is implicated in aging-related diseases, such as nonalcoholic fatty liver disease, obesity and diabetes, pulmonary hypertension, and tumorigenesis...
August 5, 2018: Journal of Cellular Physiology
Wei Xu, Yue Li, Wei-Wei Yuan, Yuan Yin, Wei-Wei Song, Yu Wang, Qi-Qing Huang, Wei-Hong Zhao, Jian-Qing Wu
BACKGROUND/AIMS: Cellular senescence acts as a barrier against tumorigenesis. The CD40L transgene, expressed in some tumor cells, not only becomes visible to antigen-presenting cells but also actively catalyzes its own termination. Here, we evaluated the effect of a membrane-bound mutant form of human CD40L (CD40L-M) on senescence and the senescence-associated secretory phenotype (SASP) in non-small cell lung cancer (NSCLC). METHODS: CD40 expression levels in the NSCLC cell lines A549/TR, A549/DDP and H460 were examined by flow cytometry...
August 3, 2018: Cellular Physiology and Biochemistry
Andrew R Mendelsohn, James Larrick
Mitochondrial-derived peptides (MDP), encoded by mitochondrial DNA play a cytoprotective role by helping preserve mitochondrial function and cell viability under stressful conditions. Humanin and its homologs and mots-c are two of several MDPs hypothesized to have anti-aging activity based on correlative studies. For example, humanin plasma levels are inversely correlated with growth hormone (GH) and (insulin-like growth factor 1) (IGF1) expression, which may promote accelerated aging. Humanin has been shown to protect cells from beta amyloid toxicity and preserve endothelial cell function in a mouse model of atherosclerosis...
July 30, 2018: Rejuvenation Research
Tereza Cindrova-Davies, Norah M E Fogarty, Carolyn J P Jones, John Kingdom, Graham J Burton
INTRODUCTION: Premature ageing has been implicated in placental dysfunction. Senescence can be activated by oxidative stress, a key intermediary in the pathophysiology of pre-eclampsia. We examined senescence markers across normal gestation, and in pathological and post-mature pregnancies. Inducers of oxidative stress were used to mimic senescence changes in term explants. METHODS: Placental samples were collected with ethical approval and informed consent: first and second trimester samples from surgical terminations; term and pre-term controls, and early-onset pre-eclampsia samples from caesarean deliveries...
August 2018: Placenta
Jin Ran Chen, Oxana P Lazarenko, HaiJun Zhao, Alexander W Alund, Kartik Shankar
Intrauterine or early postnatal high-fat diet (HFD) have substantial influences on adult offspring health; however, studies of HFD-induced maternal obesity on regulation of adult offspring bone formation are sparse. Here, we investigated the effects of HFD-induced maternal obesity on both fetal and adult offspring skeletal development. We found that HFD-induced maternal obesity significantly decreased fetal skeletal development, but enhanced fetal osteoblastic cell senescence signaling and significantly increased the expression of inflammatory factors of the senescence associated secretory phenotype (SASP) in osteo-progenitors...
July 26, 2018: Journal of Endocrinology
Ping Chen, Xiaoting Luo, Zhihui Che, Wenli Zhang, Fuchen Liu, Daisen Hou, Dongqin Yang, Jie Liu
BACKGROUND/AIMS: Regulator of cullins-1 (ROC1) is a pivotal component of cullin-RING E3 ubiquitin ligases, which help to regulate distinct cellular processes by governing the degradation of various substrates. Because the role of ROC1 in gastric cancer is largely uncharacterized, we investigated the relationship between ROC1 expression and the prognosis of gastric cancer patients and explored the biological function of ROC1 and its underlying mechanisms in gastric cancer. METHODS: Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the correlation between the carcinogenesis of gastric cancer and ROC1...
July 24, 2018: Cellular Physiology and Biochemistry
Kamila Guimarães-Pinto, Danielle Oliveira Nascimento, Antonia Corrêa-Ferreira, Alexandre Morrot, Celio G Freire-de-Lima, Marcela F Lopes, George A DosReis, Alessandra A Filardy
Trypanosoma cruzi infects and replicates within a wide variety of immune and non-immune cells. Here, we investigated early cellular responses induced in NIH-3T3 fibroblasts upon infection with trypomastigote forms of T. cruzi . We show that fibroblasts were susceptible to T. cruzi infection and started to release trypomastigotes to the culture medium after 4 days of infection. Also, we found that T. cruzi infection reduced the number of fibroblasts in 3-day cell cultures, by altering fibroblast proliferation...
2018: Frontiers in Immunology
Rekha Jakhar, Monique N H Luijten, Alex X F Wong, Bing Cheng, Ke Guo, Suat P Neo, Bijin Au, Madhura Kulkarni, Kah J Lim, Jiamila Maimaiti, Han C Chong, Elaine H Lim, Tee B K Tan, Kong W Ong, Yirong Sim, Jill S L Wong, James B K Khoo, Juliana T S Ho, Boon T Chua, Indrajit Sinha, Xiaomeng Wang, John E Connolly, Jayantha Gunaratne, Karen C Crasta
The most-commonly utilized class of chemotherapeutic agents administered as a first-line therapy are anti-mitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit anti-mitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence...
July 23, 2018: Molecular Cancer Research: MCR
Joana Catarina Macedo, Sara Vaz, Bjorn Bakker, Rui Ribeiro, Petra Lammigje Bakker, Jose Miguel Escandell, Miguel Godinho Ferreira, René Medema, Floris Foijer, Elsa Logarinho
Aneuploidy, an abnormal chromosome number, has been linked to aging and age-associated diseases, but the underlying molecular mechanisms remain unknown. Here we show, through direct live-cell imaging of young, middle-aged, and old-aged primary human dermal fibroblasts, that aneuploidy increases with aging due to general dysfunction of the mitotic machinery. Increased chromosome mis-segregation in elderly mitotic cells correlates with an early senescence-associated secretory phenotype (SASP) and repression of Forkhead box M1 (FoxM1), the transcription factor that drives G2/M gene expression...
July 19, 2018: Nature Communications
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