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Chromatin aging

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https://www.readbyqxmd.com/read/29346525/frailty-syndrome-and-genomic-instability-in-older-adults-suitability-of-the-cytome-micronucleus-assay-as-a-diagnostic-tool
#1
María Sánchez-Flores, Diego Marcos-Pérez, Laura Lorenzo-López, Ana Maseda, José C Millán-Calenti, Stefano Bonassi, Eduardo Pásaro, Blanca Laffon, Vanessa Valdiglesias
Frailty, a condition involving increased risk of disability and mortality in older adults, has emerged as a reliable way to predict the effect of aging. Genomic instability may help to anticipate recognition of frail individuals and improving frailty outcomes. Our objective was to evaluate the potential of the micronucleus (MN) frequency, evaluated in lymphocytes and buccal cells, to anticipate frailty identification and improve diagnosis reliability. Our results, from a group of older adults over 65, showed that frail individuals had significantly higher frequencies of MN in lymphocytes (19...
January 13, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29341606/hogg1-removes-solution-accessible-8-oxog-lesions-from-globally-substituted-nucleosomes-except-at-the-dyad-region
#2
Katharina Bilotti, Mary E Tarantino, Sarah Delaney
Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8-oxoG) is initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we examine hOGG1 activity on DNA packaged as it is in chromatin, in a nucleosome core particle (NCP). We use synthetic methods to generate a population of NCPs with G to 8-oxoG substitutions and evaluate the global profile of hOGG1 repair in packaged DNA. For several turns of the helix, we observe that solution-accessible 8-oxoG are sites of activity for hOGG1...
January 17, 2018: Biochemistry
https://www.readbyqxmd.com/read/29325627/epigenetic-mechanisms-underlying-nervous-system-diseases
#3
Irfan A Qureshi, Mark F Mehler
Epigenetic mechanisms act as control systems for modulating genomic structure and activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell-intrinsic signals. These dynamic processes are responsible for mediating cell- and tissue-specific gene expression and function and gene-gene and gene-environmental interactions. The major epigenetic mechanisms include DNA methylation and hydroxymethylation; histone protein posttranslational modifications, nucleosome remodeling/repositioning, and higher-order chromatin reorganization; noncoding RNA regulation; and RNA editing...
2018: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29324871/citrullinated-histone-h3-as-a-novel-prognostic-blood-marker-in-patients-with-advanced-cancer
#4
Charlotte Thålin, Staffan Lundström, Cedric Seignez, Maud Daleskog, Annika Lundström, Peter Henriksson, Thomas Helleday, Mia Phillipson, Håkan Wallén, Mélanie Demers
Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been shown to elicit harmful effects on the host, and were recently proposed to promote tumor progression and spread. Here we report significant elevations of plasma H3Cit in patients with advanced cancer compared with age-matched healthy individuals. These elevations were specific to cancer patients as no increase was observed in severely ill and hospitalized patients with a higher non-malignant comorbidity...
2018: PloS One
https://www.readbyqxmd.com/read/29317652/sirt6-dependent-cysteine-monoubiquitination-in-the-pre-set-domain-of-suv39h1-regulates-the-nf-%C3%AE%C2%BAb-pathway
#5
Irene Santos-Barriopedro, Laia Bosch-Presegué, Anna Marazuela-Duque, Carolina de la Torre, Carlota Colomer, Berta N Vazquez, Thomas Fuhrmann, Bárbara Martínez-Pastor, Wenfu Lu, Thomas Braun, Eva Bober, Thomas Jenuwein, Lourdes Serrano, Manel Esteller, Zhenbang Chen, Silvia Barceló-Batllori, Raúl Mostoslavsky, Lluis Espinosa, Alejandro Vaquero
Sirtuins are NAD+-dependent deacetylases that facilitate cellular stress response. They include SirT6, which protects genome stability and regulates metabolic homeostasis through gene silencing, and whose loss induces an accelerated aging phenotype directly linked to hyperactivation of the NF-κB pathway. Here we show that SirT6 binds to the H3K9me3-specific histone methyltransferase Suv39h1 and induces monoubiquitination of conserved cysteines in the PRE-SET domain of Suv39h1. Following activation of NF-κB signaling Suv39h1 is released from the IκBα locus, subsequently repressing the NF-κB pathway...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29303998/linking-dna-damage-and-age-related-promoter-dna-hyper-methylation-in-the-intestine
#6
Torsten Thalheim, Maria Herberg, Joerg Galle
Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Here, we explore whether and how DNA damage repair might impact on these time-dependent changes, in particular in proliferative intestinal stem cells. We introduce a 3D multiscale computer model of intestinal crypts enabling simulation of aberrant DNA and histone methylation of gene promoters during aging. We assume histone state-dependent activity of de novo DNA methyltransferases (DNMTs) and methylation-dependent binding of maintenance DNMTs to CpGs...
January 5, 2018: Genes
https://www.readbyqxmd.com/read/29300189/bcor-ccnb3-fusion-positive-sarcomas-a-clinicopathologic-and-molecular-analysis-of-36-cases-with-comparison-to-morphologic-spectrum-and-clinical-behavior-of-other-round-cell-sarcomas
#7
Yu-Chien Kao, Adepitan A Owosho, Yun-Shao Sung, Lei Zhang, Yumi Fujisawa, Jen-Chieh Lee, Leonard Wexler, Pedram Argani, David Swanson, Brendan C Dickson, Christopher D M Fletcher, Cristina R Antonescu
BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis...
October 25, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29285138/curcumin-modulates-covalent-histone-modification-and-timp1-gene-activation-to-protect-against-vascular-injury-in-a-hypertension-rat-model
#8
Jun Hu, Tingting Shen, Jun Xie, Siyang Wang, Yue He, Fu Zhu
Hypertension is a leading risk factor for morbidity and mortality. Previous studies have reported that curcumin has anti-oxidation and anti-aging effects and inhibits histone deacetylase activity. However, it is still unclear whether curcumin could protect against vascular injury induced by hypertension. Thus, the current study examined the therapeutic effects and mechanism of curcumin on vascular injury induced by hypertension in spontaneous hypertensive rats (SHRs). The present study revealed that curcumin may improve vascular structure and attenuate coronary artery pathology...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29280055/sirtuin-1-chromatin-binding-dynamics-points-to-a-common-mechanism-regulating-inflammatory-targets-in-siv-infection-and-in-the-aging-brain
#9
Nikki Bortell, Liana Basova, Julia A Najera, Brenda Morsey, Howard S Fox, Maria Cecilia Garibaldi Marcondes
Microglia and macrophages are the main non-neuronal subsets of myeloid origin in the brain, and are critical regulators in neurodegenerative disorders, where inflammation is a key factor. Since HIV infection results in neurological perturbations that are similar to those in aging, we examined microglial and infiltrating myeloid subsets in the search for changes that might resemble the ones in aging. For that, we used the SIV infection in rhesus macaques to model neuroAIDS. We found that Sirt-1, a molecule that impacts survival and health in many models, was decreased in cell preparations containing a majority of microglia and myeloid cells from the brain of infected macaques...
December 26, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29258295/therapeutic-targeting-of-ependymoma-as-informed-by-oncogenic-enhancer-profiling
#10
Stephen C Mack, Kristian W Pajtler, Lukas Chavez, Konstantin Okonechnikov, Kelsey C Bertrand, Xiuxing Wang, Serap Erkek, Alexander Federation, Anne Song, Christine Lee, Xin Wang, Laura McDonald, James J Morrow, Alina Saiakhova, Patrick Sin-Chan, Qiulian Wu, Kulandaimanuvel Antony Michaelraj, Tyler E Miller, Christopher G Hubert, Marina Ryzhova, Livia Garzia, Laura Donovan, Stephen Dombrowski, Daniel C Factor, Betty Luu, Claudia L L Valentim, Ryan C Gimple, Andrew Morton, Leo Kim, Briana C Prager, John J Y Lee, Xiaochong Wu, Jennifer Zuccaro, Yuan Thompson, Borja L Holgado, Jüri Reimand, Susan Q Ke, Adam Tropper, Sisi Lai, Senthuran Vijayarajah, Sylvia Doan, Vaidehi Mahadev, Ana Fernandez Miñan, Susanne N Gröbner, Matthias Lienhard, Marc Zapatka, Zhiqin Huang, Kenneth D Aldape, Angel M Carcaboso, Peter J Houghton, Stephen T Keir, Till Milde, Hendrik Witt, Yan Li, Chao-Jun Li, Xiu-Wu Bian, David T W Jones, Ian Scott, Sheila K Singh, Annie Huang, Peter B Dirks, Eric Bouffet, James E Bradner, Vijay Ramaswamy, Nada Jabado, James T Rutka, Paul A Northcott, Mathieu Lupien, Peter Lichter, Andrey Korshunov, Peter C Scacheri, Stefan M Pfister, Marcel Kool, Michael D Taylor, Jeremy N Rich
Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29250748/age-is-the-work-of-art-impact-of-neutrophil-and-organism-age-on-neutrophil-extracellular-trap-formation
#11
REVIEW
Weronika Ortmann, Elzbieta Kolaczkowska
Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell...
December 18, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29249357/il-10-signaling-remodels-adipose-chromatin-architecture-to-limit-thermogenesis-and-energy-expenditure
#12
Prashant Rajbhandari, Brandon J Thomas, An-Chieh Feng, Cynthia Hong, Jiexin Wang, Laurent Vergnes, Tamer Sallam, Bo Wang, Jaspreet Sandhu, Marcus M Seldin, Aldons J Lusis, Loren G Fong, Melanie Katz, Richard Lee, Stephen G Young, Karen Reue, Stephen T Smale, Peter Tontonoz
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging...
December 8, 2017: Cell
https://www.readbyqxmd.com/read/29241633/polyploidy-and-nuclear-phenotype-characteristics-of-cardiomyocytes-from-diabetic-adult-and-normoglycemic-aged-mice
#13
Isabela S Silva, Flávia G Ghiraldini, Giovana M B Veronezi, Maria Luiza S Mello
The frequency of polyploid nuclei in the aging human heart is in sharp contrast with that in the human liver. An inverse pattern exists between the mouse heart and liver cells. Ploidy degrees in mouse hepatocytes under hyperglycemic conditions are elevated to higher levels than those in aged hepatocytes. In this study, image analysis cytometry was used to investigate the effect of diabetes and aging on Feulgen-DNA quantities, ploidy degrees, nuclear shapes and chromatin texture in mouse cardiomyocytes compared to previously reported data for mouse hepatocytes...
December 11, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/29237964/myeloid-sarcoma-a-clinicopathological-study-with-emphasis-on-diagnostic-difficulties
#14
Ranjini Kudva, Vidya Monappa, Girish Solanke, Manna Valiathan, Anuradha C K Rao, V Geetha
BACKGROUND: Myeloid sarcoma (MS) is a rare tumor composed of proliferation of myeloid precursors at extramedullary sites. They can arise de-novo or in association with hematological malignancies, most commonly acute myeloid leukemia. Clinically, it can masquerade as an abscess, cutaneous ulcer, or mass lesion. Morphologically, MS can mimic a variety of small round cell tumors including lymphomas and rhabdomyosarcoma. AIMS: (1) To study the clinical presentations and laboratory findings in patients with MS; (2) to revisit the histomorphological findings and the differential diagnosis of MS; (3) to evaluate the diagnostic role of immunohistochemistry (IHC) and determine the useful markers for accurate diagnosis of MS...
October 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/29236713/sirt3-deficiency-does-not-affect-venous-thrombosis-or-netosis-despite-mild-elevation-of-intracellular-ros-in-platelets-and-neutrophils-in-mice
#15
Hideki Hayashi, Deya Cherpokova, Kimberly Martinod, Thilo Witsch, Siu Ling Wong, Maureen Gallant, Stephen M Cifuni, Leonard P Guarente, Denisa D Wagner
Inflammation is a common denominator in chronic diseases of aging. Yet, how inflammation fuels these diseases remains unknown. Neutrophils are the primary leukocytes involved in the early phase of innate immunity and inflammation. As part of their anti-microbial defense, neutrophils form extracellular traps (NETs) by releasing decondensed chromatin lined with cytotoxic proteins. NETs have been shown to induce tissue injury and thrombosis. Here, we demonstrated that Sirt3, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, an enzyme linked to human longevity, was expressed in mouse neutrophils and platelets...
2017: PloS One
https://www.readbyqxmd.com/read/29233090/dna-methylation-regulates-discrimination-of-enhancers-from-promoters-through-a-h3k4me1-h3k4me3-seesaw-mechanism
#16
Ali Sharifi-Zarchi, Daniela Gerovska, Kenjiro Adachi, Mehdi Totonchi, Hamid Pezeshk, Ryan J Taft, Hans R Schöler, Hamidreza Chitsaz, Mehdi Sadeghi, Hossein Baharvand, Marcos J Araúzo-Bravo
BACKGROUND: DNA methylation at promoters is largely correlated with inhibition of gene expression. However, the role of DNA methylation at enhancers is not fully understood, although a crosstalk with chromatin marks is expected. Actually, there exist contradictory reports about positive and negative correlations between DNA methylation and H3K4me1, a chromatin hallmark of enhancers. RESULTS: We investigated the relationship between DNA methylation and active chromatin marks through genome-wide correlations, and found anti-correlation between H3K4me1 and H3K4me3 enrichment at low and intermediate DNA methylation loci...
December 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29230532/rna-mediated-transgenerational-inheritance-in-ciliates-and-plants
#17
REVIEW
Zachary T Neeb, Mariusz Nowacki
In the age of next-generation sequencing (NGS) and with the availability of whole sequenced genomes and epigenomes, some attention has shifted from purely sequence-based studies to those of heritable epigenetic modifications. Transgenerational inheritance can be defined as heritable changes to the state of DNA that may be passed on to subsequent generations without alterations to the underlying DNA sequence. Although this phenomenon has been extensively studied in many systems, studies of transgenerational inheritance in mammals and other higher-level eukaryotes may be complicated by the fact that many epigenetic marks are reprogrammed during sexual reproduction...
December 11, 2017: Chromosoma
https://www.readbyqxmd.com/read/29220290/synovial-sarcoma-current-concepts-and-future-perspectives
#18
Silvia Stacchiotti, Brian Andrew Van Tine
Synovial sarcoma (SS) is a rare sarcoma driven by a translocation between SS18 and SSX 1, 2, or 4. With approximately 800 to 1,000 cases a year in the United States, it most commonly affects young adults between the ages of 15 and 30 years. The resultant tumors are either monophasic (pure sarcomas), biphasic (a combination or epithelioid and sarcomatous components), or poorly differentiated. The hybrid transcription factor SS18:SSX alters SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling and global methylation patterns that may allow for future therapeutic opportunities...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29219199/variable-transcriptional-responsiveness-of-the-p2%C3%A2-%C3%A3-%C3%A2-3-receptor-gene-during-cfa-induced-inflammatory-hyperalgesia
#19
Paulina Nuñez-Badinez, Hugo Sepúlveda, Emilio Diaz, Wolfgang Greffrath, Rolf-Detlef Treede, Jimmy Stehberg, Martin Montecino, Brigitte van Zundert
The purinergic receptor P2 × 3 (P2 × 3-R) plays important roles in molecular pathways of pain, and reduction of its activity or expression effectively reduces chronic inflammatory and neuropathic pain sensation. Inflammation, nerve injury, and cancer-induced pain can increase P2 × 3-R mRNA and/or protein levels in dorsal root ganglia (DRG). However, P2 × 3-R expression is unaltered or even reduced in other pain studies. The reasons for these discrepancies are unknown and might depend on the applied traumatic intervention or on intrinsic factors such as age, gender, genetic background and/or epigenetics...
December 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29208544/mandibuloacral-dysplasia-a-premature-ageing-disease-with-aspects-of-physiological-ageing
#20
REVIEW
Vittoria Cenni, Maria Rosaria D'Apice, Paolo Garagnani, Marta Columbaro, Giuseppe Novelli, Claudio Franceschi, Giovanna Lattanzi
Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone abnormalities including localized osteolysis and generalized osteoporosis, skin pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene, causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24 mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects chromatin dynamics and stress response...
December 2, 2017: Ageing Research Reviews
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