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https://www.readbyqxmd.com/read/27907906/senescent-fibroblast-derived-chemerin-promotes-squamous-cell-carcinoma-migration
#1
Vida Farsam, Abhijit Basu, Martina Gatzka, Nicolai Treiber, Lars A Schneider, Medhanie A Mulaw, Tanja Lucas, Stefan Kochanek, Reinhard Dummer, Mitchell P Levesque, Meinhard Wlaschek, Karin Scharffetter-Kochanek
Aging is associated with a rising incidence of cutaneous squamous cell carcinoma (cSCC), an aggressive skin cancer with the potential for local invasion and metastasis. Acquisition of a senescence-associated secretory phenotype (SASP) in dermal fibroblasts has been postulated to promote skin cancer progression in elderly individuals. The underlying molecular mechanisms are largely unexplored. We show that Chemerin, a previously unreported SASP factor released from senescent human dermal fibroblasts, promotes cSCC cell migration, a key feature driving tumor progression...
November 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889642/redox-control-of-senescence-and-age-related-disease
#2
REVIEW
Akshaya Chandrasekaran, Maria Del Pilar Sosa Idelchik, J Andrés Melendez
The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS) provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic pathways...
November 16, 2016: Redox Biology
https://www.readbyqxmd.com/read/27883166/effect-of-low-dose-rapamycin-on-senescence-markers-and-physical-functioning-in-older-adults-with-coronary-artery-disease-results-of-a-pilot-study
#3
M Singh, M D Jensen, A Lerman, S Kushwaha, C S Rihal, B J Gersh, A Behfar, T Tchkonia, R J Thomas, R J Lennon, L R Keenan, A G Moore, J L Kirkland
Rapamycin, an mTOR inhibitor affects senescence through suppression of senescence-associated secretory phenotype (SASP). We studied the safety and feasibility of low-dose rapamycin and its effect on SASP and frailty in elderly undergoing cardiac rehabilitation (CR). 13 patients; 6 (0.5mg), 6 (1.0mg), and 1 patient received 2mg oral rapamycin (serum rapamycin <6ng/ml) daily for 12 weeks. Median age was 73.9±7.5 years and 12 were men. Serum interleukin-6 decreased (2.6 vs 4.4 pg/ml) and MMP-3 (26 vs 23.5 ng/ml) increased...
2016: Journal of Frailty & Aging
https://www.readbyqxmd.com/read/27867017/genomic-amplification-of-fanconi-anemia-complementation-group-a-fanca-in-head-and-neck-squamous-cell-carcinoma-hnscc-cellular-mechanisms-of-radioresistance-and-clinical-relevance
#4
Julia Hess, Kristian Unger, Michael Orth, Ulrike Schötz, Lars Schüttrumpf, Verena Zangen, Igor Gimenez-Aznar, Agata Michna, Ludmila Schneider, Ramona Stamp, Martin Selmansberger, Herbert Braselmann, Ludwig Hieber, Guido A Drexler, Sebastian Kuger, Diana Klein, Verena Jendrossek, Anna A Friedl, Claus Belka, Horst Zitzelsberger, Kirsten Lauber
Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance...
November 17, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27856491/excavating-the-surface-associated-and-secretory-proteome-of-mycobacterium-leprae-for-identifying-vaccines-and-diagnostic-markers-relevant-immunodominant-epitopes
#5
Aarti Rana, Shweta Thakur, Nupur Bhardwaj, Devender Kumar, Yusuf Akhter
For centuries Mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live attenuated vaccines and antibiotics. Surface-associated and secretory proteins (SASPs) are attractive targets against bacteria. We have integrated biological knowledge with computational approaches and present a proteome-wide identification of SASPs. We also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidates in most important class of SASPs, the outer membrane proteins (OMPs)...
November 16, 2016: Pathogens and Disease
https://www.readbyqxmd.com/read/27856124/enhanced-molecular-aging-in-late-life-depression-the-senescent-associated-secretory-phenotype
#6
Breno Satler Diniz, Charles F Reynolds, Etienne Sibille, Chien-Wei Lin, George Tseng, Francis Lotrich, Howard J Aizenstein, Meryl A Butters
OBJECTIVE: This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants. DESIGN: Cross-sectional study. PARTICIPANTS: We included 111 older adults (80 with LLD and 31 comparison participants) in this study. MEASUREMENT: A panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants...
August 31, 2016: American Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/27849057/cell-senescence-is-an-antiviral-defense-mechanism
#7
Maite Baz-Martínez, Sabela Da Silva-Álvarez, Estefanía Rodríguez, Jorge Guerra, Ahmed El Motiam, Anxo Vidal, Tomás García-Caballero, Miguel González-Barcia, Laura Sánchez, César Muñoz-Fontela, Manuel Collado, Carmen Rivas
Cellular senescence is often considered a protection mechanism triggered by conditions that impose cellular stress. Continuous proliferation, DNA damaging agents or activated oncogenes are well-known activators of cell senescence. Apart from a characteristic stable cell cycle arrest, this response also involves a proinflammatory phenotype known as senescence-associated secretory phenotype (SASP). This, together with the widely known interference with senescence pathways by some oncoviruses, had led to the hypothesis that senescence may also be part of the host cell response to fight virus...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27842816/dimethyl-%C3%AE-cyclodextrin-salazosulfapyridine-inclusion-complex-loaded-chitosan-nanoparticles-for-sustained-release
#8
Peixiao Tang, Hongqin Yang, Bin Tang, Di Wu, Qiaohong Du, Kailin Xu, Hui Li
This study aimed to investigate a novel delivery system for salazosulfapyridine (SASP) through encapsulation in 2,6-dimethyl-β-cyclodextrin (DMβCD) and further incorporation in chitosan (CS) to form nanoparticles (NPs). The inclusion complex of SASP and DMβCD was prepared at 1:1 host-guest stoichiometry based on Job's plot and then characterized through various analytical techniques. Then, the DMβCD/SASP inclusion complex was incorporated in CS to form DMβCD/SASP/CS NPs. The loading efficiency of SASP in the DMβCD/SASP/CS NPs was significantly higher than that of the SASP/CS NPs...
January 20, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/27831553/reed-sternberg-cells-in-hodgkin-s-lymphoma-present-features-of-cellular-senescence
#9
J Gopas, E Stern, U Zurgil, J Ozer, A Ben-Ari, G Shubinsky, A Braiman, R Sinay, J Ezratty, V Dronov, S Balachandran, D Benharroch, E Livneh
Hodgkin's Lymphoma (HL) is one of the most prevailing malignancies in young adults. Reed-Sternberg (RS) cells in HL have distinctive large cell morphology, are characteristic of the disease and their presence is essential for diagnosis. Enlarged cells are one of the hallmarks of senescence, but whether RS cells are senescent has not been previously investigated. Here we show that RS cells have characteristics of senescent cells; RS cells in HL biopsies specifically express the senescence markers and cell cycle inhibitors p21(Cip1) and p16(INK4a) and are negative for the proliferation marker Ki-67, suggesting that these cells have ceased to proliferate...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27812882/induction-and-detection-of-oncogene-induced-cellular-senescence-in-drosophila
#10
Mai Nakamura, Tatsushi Igaki
Cellular senescence is induced by various cellular stresses, including activation of the Ras oncogene. In Drosophila imaginal epithelia, clones of cells expressing oncogenic Ras (Ras(V12)) show several markers of cellular senescence, such as elevation of SA-β-gal activity, upregulation of the Cdk inhibitor Dacapo (Dap), and heterochromatinization. However, these cells do not undergo cell cycle arrest or exhibit a DNA damage response (DDR), cellular hypertrophy, or a senescence-associated secretory phenotype (SASP), other essential markers of cellular senescence...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27812871/detecting-the-senescence-associated-secretory-phenotype-sasp-by-high-content-microscopy-analysis
#11
Priya Hari, Juan Carlos Acosta
The diverse arrays of proteins secreted by senescent cells have been described to influence aging and to have both pro-tumorigenic and anti-tumorigenic influences on the surrounding microenvironment. Further characterization of these proteins, known as the senescence-associated secretory phenotype (SASP), and their regulators is required to understand and further manipulate such activities. The use of high-throughput technology allows us to obtain visual and quantitative data on a large number of samples quickly and easily...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27799373/hmgb2-holds-the-key-to-the-senescence-associated-secretory-phenotype
#12
Ana Guerrero, Jesús Gil
The senescence-associated secretory phenotype (SASP) is a hallmark of senescence with an important physiological impact, but how it is established is unclear. In this issue, Aird et al. (2016. J. Cell Biol. https://doi.org/10.1083/jcb.201608026) describe how chromatin-bound HMGB2 fine tunes SASP expression by avoiding heterochromatin spreading.
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27799366/hmgb2-orchestrates-the-chromatin-landscape-of-senescence-associated-secretory-phenotype-gene-loci
#13
Katherine M Aird, Osamu Iwasaki, Andrew V Kossenkov, Hideki Tanizawa, Nail Fatkhutdinov, Benjamin G Bitler, Linh Le, Gretchen Alicea, Ting-Lin Yang, F Brad Johnson, Ken-Ichi Noma, Rugang Zhang
Cellular senescence is a stable cell growth arrest that is characterized by the silencing of proliferation-promoting genes through compaction of chromosomes into senescence-associated heterochromatin foci (SAHF). Paradoxically, senescence is also accompanied by increased transcription of certain genes encoding for secreted factors such as cytokines and chemokines, known as the senescence-associated secretory phenotype (SASP). How SASP genes are excluded from SAHF-mediated global gene silencing remains unclear...
November 7, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27797960/senescence-associated-secretory-phenotype-contributes-to-pathological-angiogenesis-in-retinopathy
#14
Malika Oubaha, Khalil Miloudi, Agnieszka Dejda, Vera Guber, Gaëlle Mawambo, Marie-Anne Germain, Guillaume Bourdel, Natalija Popovic, Flavio A Rezende, Randal J Kaufman, Frédérick A Mallette, Przemyslaw Sapieha
Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions of the retina showed only modest rates of apoptosis despite severely compromised metabolic supply. Using transcriptomic analysis and inducible loss-of-function genetics, we demonstrated that ischemic retinal cells instead engage the endoplasmic reticulum stress inositol-requiring enzyme 1α (IRE1α) pathway that, through its endoribonuclease activity, induces a state of senescence in which cells adopt a senescence-associated secretory phenotype (SASP)...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27764549/notch-and-the-2-sasps-of-senescence
#15
Matthew Hoare, Masashi Narita
No abstract text is available yet for this article.
October 20, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27752926/ccn2-induces-cellular-senescence-in-fibroblasts
#16
Joon-Ii Jun, Lester F Lau
The expression of Ccn2 (CTGF) has been linked to fibrosis in many tissues and pathologies, although its activities in fibroblastic cells and precise mechanism of action in fibrogenesis are still controversial. Here, we showed that CCN2 can induce cellular senescence in fibroblasts both in vitro and in vivo, whereupon senescent cells express an anti-fibrotic "senescence-associated secretory phenotype" (SASP) that includes upregulation of matrix metalloproteinases and downregulation of collagen. Mechanistically, CCN2 induces fibroblast senescence through integrin α6β1-mediated accumulation of reactive oxygen species, leading to activation of p53 and induction of p16(INK4a)...
October 18, 2016: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/27734200/increase-in-tumor-suppressor-arf-compensates-gene-dysregulation-in-in-vitro-aged-adipocytes
#17
Arif U Hasan, Koji Ohmori, Takeshi Hashimoto, Kazuyo Kamitori, Fuminori Yamaguchi, Kumi Konishi, Takahisa Noma, Junsuke Igarashi, Tetsuo Yamashita, Katsuya Hirano, Masaaki Tokuda, Tetsuo Minamino, Akira Nishiyama, Masakazu Kohno
Deterioration of adipocyte function due to increased oxidative stress predisposes patients to metabolic disorders in advanced age. However, the roles of tumor suppressors in such conditions remain largely unknown. Therefore, we aimed to address their dynamics in aged adipocytes using a long-term culture model. We compared 3T3-L1 adipocytes at 17-19 days (long-term) with those at 8-10 days (short-term) after initiation of adipogenic induction for mimicking 'aged' and 'young' adipocytes, respectively. H2O2 release and dihydroethidium (DHE) staining was increased, while superoxide dismutase (SOD) activity was reduced in long-term cultured adipocytes, which is suggestive of enhanced oxidative stress in this group...
October 12, 2016: Biogerontology
https://www.readbyqxmd.com/read/27732890/autophagy-deficient-melanocytes-display-a-senescence-associated-secretory-phenotype-that-includes-oxidized-lipid-mediators
#18
Chunya Ni, Marie-Sophie Narzt, Ionela-Mariana Nagelreiter, Cheng Feng Zhang, Lionel Larue, Heidemarie Rossiter, Johannes Grillari, Erwin Tschachler, Florian Gruber
Autophagy is a recycling program which allows cells to adapt to metabolic needs and to stress. Defects in autophagy can affect metabolism, aging, proteostasis and inflammation. Autophagy pathway genes, including autophagy related 7 (Atg7), have been associated with the regulation of skin pigmentation, and autophagy defects disturb the biogenesis and transport of melanosomes in melanocytes as well as transfer and processing of melanin into keratinocytes. We have previously shown that mice whose melanocytes or keratinocytes lack Atg7 (and thus autophagy) as a result of specific gene knockout still retained functioning melanosome synthesis and transfer, and displayed only moderate reduction of pigmentation...
October 9, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27731420/whole-chromosome-instability-induces-senescence-and-promotes-sasp
#19
Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna
Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs)...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27673450/aspl-tfe3-oncoprotein-regulates-cell-cycle-progression-and-induces-cellular-senescence-by-up-regulating-p21
#20
Naoko Ishiguro, Haruhiko Yoshida
Alveolar soft part sarcoma is an extremely rare soft tissue sarcoma with poor prognosis. It is characterized by the unbalanced recurrent chromosomal translocation der(17)t(X;17)(p11;q25), resulting in the generation of an ASPL-TFE3 fusion gene. ASPL-TFE3 oncoprotein functions as an aberrant transcriptional factor and is considered to play a crucial role in the tumorigenesis of alveolar soft part sarcoma. However, the underlying molecular mechanisms are poorly understood. In this study, we identified p21 (p21(WAF1/CIP1)) as a direct transcriptional target of ASPL-TFE3...
October 2016: Neoplasia: An International Journal for Oncology Research
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