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Senescence

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https://www.readbyqxmd.com/read/28340347/rejuvenation-by-therapeutic-elimination-of-senescent-cells
#1
Paul Krimpenfort, Anton Berns
In this issue of Cell, Baar et al. show how FOXO4 protects senescent cell viability by keeping p53 sequestered in nuclear bodies, preventing it from inducing apoptosis. Disrupting this interaction with an all-D amino acid peptide (FOXO4-DRI) restores p53's apoptotic role and ameliorates the consequences of senescence-associated loss of tissue homeostasis.
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340339/targeted-apoptosis-of-senescent-cells-restores-tissue-homeostasis-in-response-to-chemotoxicity-and-aging
#2
Marjolein P Baar, Renata M C Brandt, Diana A Putavet, Julian D D Klein, Kasper W J Derks, Benjamin R M Bourgeois, Sarah Stryeck, Yvonne Rijksen, Hester van Willigenburg, Danny A Feijtel, Ingrid van der Pluijm, Jeroen Essers, Wiggert A van Cappellen, Wilfred F van IJcken, Adriaan B Houtsmuller, Joris Pothof, Ron W F de Bruin, Tobias Madl, Jan H J Hoeijmakers, Judith Campisi, Peter L J de Keizer
The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340313/linkage-between-mitochondrial-genome-alterations-telomere-length-and-aging-population
#3
Egija Zole, Krista Zadinane, Liana Pliss, Renate Ranka
We studied telomere length (TL) and mitochondrial DNA (mtDNA) copy number variations in individuals from Latvian Caucasian population in different age groups. We showed a positive correlation between TL and mtDNA copy number in individuals of up to 90 years of age; however, this correlation was not observed in the 90-100 years age group. While TL shortened with age and mtDNA content decreased with increasing age, in this study it was observed that mtDNA copy number in nonagenarians was slightly higher than in the 60-89 years age group...
March 24, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28340212/accelerated-senescence-in-skin-in-a-murine-model-of-radiation-induced-multi-organ-injury
#4
Elizabeth A McCart, Rajesh L Thangapazham, Eric D Lombardini, Steven R Mog, Ronald Allan M Panganiban, Kelley M Dickson, Rihab A Mansur, Vitaly Nagy, Sung-Yop Kim, Reed Selwyn, Michael R Landauer, Thomas N Darling, Regina M Day
Accidental high-dose radiation exposures can lead to multi-organ injuries, including radiation dermatitis. The types of cellular damage leading to radiation dermatitis are not completely understood. To identify the cellular mechanisms that underlie radiation-induced skin injury in vivo, we evaluated the time-course of cellular effects of radiation (14, 16 or 17 Gy X-rays; 0.5 Gy/min) in the skin of C57BL/6 mice. Irradiation of 14 Gy induced mild inflammation, observed histologically, but no visible hair loss or erythema...
March 18, 2017: Journal of Radiation Research
https://www.readbyqxmd.com/read/28340115/cellular-senescence-in-mouse-hippocampus-after-irradiation-and-the-role-of-p53-and-p21
#5
Zoey Cheng, Yan Zhen Zheng, Yu-Qing Li, C Shun Wong
Diverse stress signals including irradiation may trigger cellular senescence. We asked whether irradiation induced senescence in mouse hippocampus, and whether p53 or p21 played a role in this response. Following whole-brain irradiation, polymerase chain reaction (PCR) arrays for senescence-associated genes showed increased expression of CDKN1A (p21) and CDKN2A (p19ARF) in mouse hippocampus at 9 weeks. Upregulation of p21 and p19ARF was confirmed using real-time PCR, which also demonstrated increased CDKN2A/p16INKa expression after irradiation...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28339869/alcohol-induces-cellular-senescence-and-impairs-osteogenic-potential-in-bone-marrow-derived-mesenchymal-stem-cells
#6
Xi Chen, Mao Li, Jinku Yan, Tao Liu, Guoqing Pan, Huilin Yang, Ming Pei, Fan He
Aims: Chronic and excessive alcohol consumption is a high-risk factor for osteoporosis. Bone marrow-derived mesenchymal stem cells (BM-MSCs) play an important role in bone formation; however, they are vulnerable to ethanol (EtOH). The purpose of this research was to investigate whether EtOH could induce premature senescence in BM-MSCs and subsequently impair their osteogenic potential. Methods: Human BM-MSCs were exposed to EtOH ranging from 10 to 250 mM. Senescence-associated β-galactosidase (SA-β-gal) activity, cell cycle distribution, cell proliferation and reactive oxygen species (ROS) were evaluated...
February 25, 2017: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
https://www.readbyqxmd.com/read/28339060/chronological-changes-in-the-expression-of-phosphorylated-tau-and-5%C3%A2-amp%C3%A2-activated-protein-kinase-in-the-brain-of-senescence%C3%A2-accelerated-p8-mice
#7
Hak-Su Kim, Sohee Moon, Sujin Kim, Min-Jae Lee, Min Hwa Suk, Dong-Ho Park, Dong Wun Shin, Chang-Shin Park, Ju-Hee Kang
Senescence-accelerated mouse prone 8 (SAMP8), a non‑transgenic animal model used for researching sporadic Alzheimer's disease (AD), presents AD pathologies and overall dysregulation in brain energy metabolism, which is one of the early pathogenic characteristics of AD. In the present study, the authors examined chronological changes in the expression patterns of phosphorylated tau and of proteins related to energy metabolism to evaluate the association of tau phosphorylation and metabolism, using young‑ (2‑months‑old), middle‑ (5‑months‑old) and old‑aged (10‑months‑old) SAMP8...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339038/lncrna%C3%A2-mediated-sirt1-foxo3a-and-sirt1-p53-signaling-pathways-regulate-type-ii-alveolar-epithelial-cell-senescence-in-patients-with-chronic-obstructive-pulmonary-disease
#8
Chao Gu, Yaqing Li, Jialiang Liu, Xiwang Ying, Yuanshun Liu, Jianping Yan, Chun Chen, Hongbin Zhou, Liming Cao, Yingyu Ma
The loss of alveolar structure and airspace enlargement are major pathological changes in chronic obstructive pulmonary disease (COPD). Type II alveolar epithelial cells (AECII) are involved in maintaining lung tissue repair and alveolar homeostasis. Long non‑coding RNAs (lncRNAs) are involved in multi‑regulating gene transcription, affecting processes including embryonic development, cell differentiation and cellular senescence. The primary aim of the present study was to explore the mechanisms of AECII senescence regulated by lncRNA‑mediated sirtuin 1 (SIRT1) and forkhead box O 3a (FoxO3a) signaling pathways in patients with COPD...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338833/a-humidity-shock-leads-to-rapid-temperature-dependent-changes-in-coffee-leaf-physiology-and-gene-expression
#9
El-Hadji Thioune, James McCarthy, Thomas Gallagher, Bruce Osborne
Climate change is expected to increase the frequency of above-normal atmospheric water deficits contemporaneous with periods of high temperatures. Here we explore alterations in physiology and gene expression in leaves of Coffea canephora Pierre ex A. Froehner caused by a sharp drop in relative humidity (RH) at three different temperatures. Both stomatal conductance (gs) and CO2 assimilation (A) measurements showed that gs and A values fell quickly at all temperatures after the transfer to low RH.  However, leaf relative water content measurements indicated that leaves nonetheless experienced substantial water losses, implying that stomatal closure and/or resupply of water was not fast enough to stop excessive evaporative losses...
February 8, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28338822/gene-expression-atlas-of-pigeonpea-and-its-application-to-gain-insights-into-genes-associated-with-pollen-fertility-implicated-in-seed-formation
#10
Lekha T Pazhamala, Shilp Purohit, Rachit K Saxena, Vanika Garg, L Krishnamurthy, Jerome Verdier, Rajeev K Varshney
Pigeonpea (Cajanus cajan) is an important grain legume of the semi-arid tropics, mainly used for its protein rich seeds. To link the genome sequence information with agronomic traits resulting from specific developmental processes, a Cajanus cajan gene expression atlas (CcGEA) was developed using the Asha genotype. Thirty tissues/organs representing developmental stages from germination to senescence were used to generate 590.84 million paired-end RNA-Seq data. The CcGEA revealed a compendium of 28 793 genes with differential, specific, spatio-temporal and constitutive expression during various stages of development in different tissues...
February 23, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28338770/response-of-human-non-small-cell-lung-cancer-cells-to-the-influence-of-wogonin-with-sgk1-dynamics
#11
Guanglin Shi, Qian Wang, Xiaoyu Zhou, Jun Li, Hua Liu, Jun Gu, Haiying Wang, Yi Wu, Liang Ding, Songshi Ni, Zhiyuan Tang
A number of significant studies in the field of cell biology have revealed another pattern of intracellular signal transduction in which cells transmit information through the dynamics of key signaling molecules. Dynamical properties of p53 have been demonstrated to be the key factor in dictating cell fate, including cell cycle arrest, permanent cell cycle arrest, and cell death. Previous studies showed a negative feedback regulation pathway between SGK1 and p53, but the dynamics of SGK1 have never been reported before...
February 18, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28338757/acceleration-of-leaf-senescence-is-slowed-down-in-transgenic-barley-plants-deficient-in-the-dna-rna-binding-protein-whirly1
#12
Weronika Kucharewicz, Assaf Distelfeld, Wolfgang Bilger, Maren Müller, Sergi Munné-Bosch, Götz Hensel, Karin Krupinska
WHIRLY1 in barley was isolated as a potential regulator of the senescence-associated gene HvS40. In order to investigate whether the plastid-nucleus-located DNA/RNA-binding protein WHIRLY1 plays a role in regulation of leaf senescence, primary foliage leaves from transgenic barley plants with an RNAi-mediated knockdown of the WHIRLY1 gene were characterized by typical senescence parameters, namely pigment contents, function and composition of the photosynthetic apparatus, as well as expression of selected genes known to be either down- or up-regulated during leaf senescence...
January 28, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28338178/the-involvement-of-senescence-induced-by-the-telomere-shortness-in-the-decline-of-osteogenic-differentiation-in-bmscs
#13
C Li, G-J Wei, L Xu, J-S Rong, S-Q Tao, Y-S Wang
OBJECTIVE: BMSC (Bone marrow mesenchymal stem cells) is an important seed cell for the repair of bone and cartilage defect in the tissue engineering. The proliferation rate and differentiation capacity of BMSCs from the old donors were less than that from young donors; however, the related mechanism remained unclear. MATERIALS AND METHODS: Sprague Dawley (SD) rats BMSCs were cultured and treated. Hydrogen peroxide (H2O2) and continual passage of BMSCs were performed to induce senescence...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28336912/fgf21-regulates-t-cell-development-in-the-neonatal-and-juvenile-thymus
#14
Yoshiaki Nakayama, Yuki Masuda, Hiroya Ohta, Tomohiro Tanaka, Miwa Washida, Yo-Ichi Nabeshima, Ayumi Miyake, Nobuyuki Itoh, Morichika Konishi
We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4(+) and CD8(+) thymocytes without obvious alteration in TECs...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28336486/mitochondrial-dysfunction-in-airway-disease
#15
Y S Prakash, Christina M Pabelick, Gary C Sieck
There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore non-canonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke and environmental insults important in these diseases, and in turn can respond to such stimuli via altered mitochondrial protein expression, structure, and resultant dysfunction...
March 21, 2017: Chest
https://www.readbyqxmd.com/read/28336395/human-immune-compartment-comparisons-optimization-of-proliferative-assays-for-blood-and-gut-t-lymphocytes
#16
Jeffrey Dock, Lance Hultin, Patricia Hultin, Julie Elliot, Otto O Yang, Peter A Anton, Beth D Jamieson, Rita B Effros
The accumulation of peripheral blood late-differentiated memory CD8 T cells with features of replicative (cellular) senescence, including inability to proliferate in vitro, has been extensively studied. Importantly, the abundance of these cells is directly correlated with increased morbidity and mortality in older persons. Of note, peripheral blood contains only 2% of the total body lymphocyte population. By contrast, the gut-associated lymphoid tissue (GALT) is the most extensive lymphoid organ, housing up to 60% of total body lymphocytes, but has never been assessed with respect to senescence profiles...
March 20, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28336372/doxorubicin-targets-multiple-players-a-new-view-of-an-old-problem
#17
REVIEW
Donato Cappetta, Francesca Rossi, Elena Piegari, Federico Quaini, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
Anthracycline cardiotoxicity remains a serious problem in paediatric and adult cancer survivors, and the advancement of cardio-oncology is a necessary step for an effective care of the patients that experience adverse cardiovascular effects. In this review, we discuss the multiple instruments used by clinicians that constitute the current strategies for primary and secondary prevention aiming at contrasting the onset of early and late doxorubicin-induced cardiotoxic events. The importance of early detection of cardiotoxicity and the following pharmacological therapy has been acknowledged with the emphasis put on impaired diastolic function, an increasingly recognized precocious sign of doxorubicin cardiotoxicity with an emerging scientific and clinical interest...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336215/association-of-increased-levels-of-mcp-1-and-cathepsin-d-in-young-onset-type-2-diabetes-patients-t2dm-y-with-severity-of-diabetic-retinopathy
#18
Sruthi Reddy, Anandakumar Amutha, Ramachandran Rajalakshmi, Regin Bhaskaran, Finny Monickaraj, Sampathkumar Rangasamy, Ranjit Mohan Anjana, Shiny Abhijit, Kuppan Gokulakrishnan, Arup Das, Viswanathan Mohan, Muthuswamy Balasubramanyam
AIM: Young onset type 2 diabetes patients (T2DM-Y) have been shown to possess an increased risk of developing microvascular complications particularly diabetic retinopathy. However, the molecular mechanisms are not clearly understood. In this study, we investigated the serum levels of monocyte chemotactic protein 1 (MCP-1) and cathepsin-D in patients with T2DM-Y without and with diabetic retinopathy. METHODS: In this case-control study, participants comprised individuals with normal glucose tolerance (NGT=40), patients with type 2 diabetes mellitus (T2DM=35), non-proliferative diabetic retinopathy (NPDR=35) and proliferative diabetic retinopathy (PDR=35)...
March 10, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28334197/ppar%C3%AE-regulates-tumor-cell-proliferation-and-senescence-via-a-novel-target-gene-carnitine-palmitoyltransferase-1c
#19
Yixin Chen, Yongtao Wang, Yaoyao Huang, Hang Zeng, Bingfang Hu, Lihuan Guan, Huizhen Zhang, Ai-Ming Yu, Caroline H Johnson, Frank J Gonzalez, Min Huang, Huichang Bi
Carnitine palmitoyltransferase 1C (CPT1C), an enzyme located in the outer mitochondria membrane, has a crucial role in fatty acid transport and oxidation. It is also involved in cell proliferation and is a potential driver for cancer cell senescence. However, its upstream regulatory mechanism is unknown. Peroxisome proliferator activated receptor α (PPARα) is a ligand-activated transcription factor that regulates lipid metabolism and tumor progression. The current study aimed to elucidate whether and how PPARα regulates CPT1C and then affects cancer cell proliferation and senescence...
March 3, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28334019/cell-survival-and-differentiation-with-nanocrystalline-glass-like-carbon-using-substantia-nigra-dopaminergic-cells-derived-from-transgenic-mouse-embryos
#20
Noela Rodriguez-Losada, Pablo Romero, Guillermo Estivill-Torrús, Roberto Guzmán de Villoria, Jose A Aguirre
Regenerative medicine requires, in many cases, physical supports to facilitate appropriate cellular architecture, cell polarization and the improvement of the correct differentiation processes of embryonic stem cells, induced pluripotent cells or adult cells. Because the interest in carbon nanomaterials has grown within the last decade in light of a wide variety of applications, the aim of this study was to test and evaluate the suitability and cytocompatibility of a particular nanometer-thin nanocrystalline glass-like carbon film (NGLC) composed of curved graphene flakes joined by an amorphous carbon matrix...
2017: PloS One
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