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Epigenetic Age

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https://www.readbyqxmd.com/read/28432085/acute-myeloid-leukaemia-in-a-case-with-tatton-brown-rahman-syndrome-the-peculiar-dnmt3a-r882-mutation
#1
Iris H I M Hollink, Ans M W van den Ouweland, H Berna Beverloo, Susan T C J M Arentsen-Peters, C Michel Zwaan, Anja Wagner
BACKGROUND: Recently a novel syndromic form of overgrowth with intellectual disability and distinct facial features was identified caused by constitutional mutations in the epigenetic regulator DNA-methyltransferase 3A (DNMT3A), referred to as Tatton-Brown-Rahman syndrome (TBRS). Somatically acquired mutations in DNMT3A occur in haematological malignancies and are frequently present in acute myeloid leukaemia (AML) affecting in more than 50% the arginine residue at position 882 (R882)...
April 21, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28428831/cord-blood-hematopoietic-cells-from-preterm-infants-display-altered-dna-methylation-patterns
#2
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
BACKGROUND: Premature infants are highly vulnerable to infection. This is partly attributable to the preterm immune system, which differs from that of the term neonate in cell composition and function. Multiple studies have found differential DNA methylation (DNAm) between preterm and term infants' cord blood; however, interpretation of these studies is limited by the confounding factor of blood cell composition. This study evaluates the epigenetic impact of preterm birth in isolated hematopoietic cell populations, reducing the concern of cell composition differences...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#3
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28426276/integrative-epigenetic-and-genetic-pan-cancer-somatic-alteration-portraits
#4
Lucas A Salas, Kevin C Johnson, Devin C Koestler, Dylan E O'Sullivan, Brock C Christensen
Genetic and epigenetic alterations are required for carcinogenesis and the mutation burden across tumor types has been investigated. Here, we investigate epigenetic alterations with a novel measure of global DNA methylation dysregulation, the methylation dysregulation index (MDI), across 14 cancer types in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701) from each tumor site...
April 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28423572/acceleration-of-leukocytes-epigenetic-age-as-an-early-tumor-and-sex-specific-marker-of-breast-and-colorectal-cancer
#5
Danielle Fernandes Durso, Maria Giulia Bacalini, Claudia Sala, Chiara Pirazzini, Elena Marasco, Massimiliano Bonafé, Ítalo Faria do Valle, Davide Gentilini, Gastone Castellani, Ana Maria Caetano Faria, Claudio Franceschi, Paolo Garagnani, Christine Nardini
Changes in blood epigenetic age have been associated with several pathological conditions and have recently been described to anticipate cancer development. In this work, we analyze a publicly available leukocytes methylation dataset to evaluate the relation between DNA methylation age and the prospective development of specific types of cancer. We calculated DNA methylation age acceleration using five state-of-the-art estimators (three multi-site: Horvath, Hannum, Weidner; and two CpG specific: ELOV2 and FHL2) in a cohort including 845 subjects from the EPIC-Italy project and we compared 424 samples that remained cancer-free over the approximately ten years of follow-up with 235 and 166 subjects who developed breast and colorectal cancer, respectively...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423456/progesterone-resistance-in-endometriosis-origins-consequences-and-interventions
#6
Bansari G Patel, Martin Rudnicki, Jie Yu, Yimin Shu, Robert N Taylor
Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis...
April 19, 2017: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/28421459/rapid-progression-to-glioblastoma-in-a-subset-of-idh-mutated-astrocytomas-a-genome-wide-analysis
#7
Timothy E Richardson, Matija Snuderl, Jonathan Serrano, Matthias A Karajannis, Adriana Heguy, Dwight Oliver, Jack M Raisanen, Elizabeth A Maher, Edward Pan, Samuel Barnett, Chunyu Cai, Amyn A Habib, Robert M Bachoo, Kimmo J Hatanpaa
According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#8
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28419547/perinatal-dna-methylation-at-cdkn2a-is-associated-with-offspring-bone-mass-findings-from-the-southampton-women-s-survey
#9
Elizabeth M Curtis, Robert Murray, Philip Titcombe, Eloïse Cook, Rebecca Clarke-Harris, Paula Costello, Emma Garratt, Joanna D Holbrook, Sheila Barton, Hazel Inskip, Keith M Godfrey, Christopher G Bell, Cyrus Cooper, Karen A Lillycrop, Nicholas C Harvey
Poor intrauterine and childhood growth has been linked with the risk of osteoporosis in later life, a relationship which may in part be mediated through altered epigenetic regulation of genes. We previously identified a region within the promoter of the long non-coding RNA ANRIL encoded by the CDKN2A locus, at which differential DNA methylation at birth showed correlations with offspring adiposity. Given the common lineage of adipocytes and osteoblasts, we investigated the relationship between perinatal CDKN2A methylation and bone mass at ages 4 and 6 years...
April 17, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28419081/prepubertal-children-born-large-for-gestational-age-have-lower-serum-dheas-concentrations-than-those-with-a-lower-birth-weight
#10
Henrikki Nordman, Raimo Voutilainen, Leena Antikainen, Jarmo Jääskeläinen
BACKGROUND: Children born small for gestational age (SGA) have higher serum dehydroepiandrosterone sulfate (DHEAS) concentrations than children born appropriate for gestational age (AGA). The overall metabolic risk associated with birth weight is U-shaped, but it is not known if children born large for gestational age (LGA) have elevated serum DHEAS levels. METHODS: A cohort of 49 LGA, 56 AGA, and 23 SGA children were studied at 5-8 years of age. Anthropometric data at birth, at the age of two years, and at examination were recorded...
April 18, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28416947/dna-methylation-profiles-of-blood-cells-are-distinct-between-early-onset-obese-and-control-individuals
#11
Je-Keun Rhee, Jin-Hee Lee, Hae Kyung Yang, Tae-Min Kim, Kun-Ho Yoon
Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416029/the-health-outcomes-of-human-offspring-conceived-by-assisted-reproductive-technologies-art
#12
M Chen, L K Heilbronn
Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health...
April 18, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28414025/alterations-of-the-translation-apparatus-during-aging-and-stress-response
#13
REVIEW
Yulia Gonskikh, Norbert Polacek
Aging is a biological process characterized by the irreversible and time-dependent deterioration of cell functions, tissues, and organs. Accumulating studies in a wide range of species from yeast to human revealed changes associated with the aging process to be conserved throughout evolution. The main characteristics of aging are (i) genomic instability, (ii) loss of telomere function, (iii) epigenetic changes,(iv) increased cellular senescence, (v) depletion of the stem cell pool, (vi) altered intercellular communication and (vii) loss of protein homeostasis...
April 13, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28411961/nutrition-in-the-first-1000-days-and-respiratory-health-a-descriptive-review-of-the-last-five-years-literature
#14
REVIEW
E Verduci, A Martelli, V L Miniello, M Landi, B Mariani, M Brambilla, L Diaferio, D G Peroni
The aim of this paper is to discuss the current evidence regarding short and long-term health respiratory effects of nutrients and dietary patterns during the first 1000 days from conception. Population of interest included children from birth to two years and their mothers (during pregnancy and lactation). Studies were searched on MEDLINE® and Cochrane database, inserting individually and using the Boolean ANDs and ORs, 'nutrients', 'micronutrients', 'LC-PUFA', 'Mediterranean Diet', 'human milk', 'complementary food', 'pregnancy', 'respiratory disease', 'pulmonary disease', 'asthma', 'epigenetics', 'first 1000 days', 'maternal diet' and 'respiratory health'...
April 12, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/28409505/dynamic-changes-in-dna-demethylation-in-the-tree-shrew-tupaia-belangeri-chinensis-brain-during-postnatal-development-and-aging
#15
Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum...
March 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28408391/lmna-associated-partial-lipodystrophy-anticipation-of-metabolic-complications
#16
Isabelle Jeru, Camille Vatier, Marie-Christine Vantyghem, Olivier Lascols, Corinne Vigouroux
BACKGROUND: Type-2 familial partial lipodystrophy (FPLD2) is a rare autosomal dominant lipodystrophic disorder due to mutations in LMNA encoding lamin A/C, a key epigenetic regulator. FPLD2 severity is determined by the occurrence of metabolic complications, especially diabetes and hypertriglyceridaemia. We evaluated the disease history and severity over generations. METHODS: This retrospective study of the largest cohort of patients with FPLD2 reported to date investigates 85 patients from 24 families comprising three generations (G1: n=39; G2: n=41; G3: n=5)...
April 13, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28405140/diet-and-microbiota-in-inflammatory-bowel-disease-the-gut-in-disharmony
#17
REVIEW
Davy C M Rapozo, Claudio Bernardazzi, Heitor Siffert Pereira de Souza
Bacterial colonization of the gut shapes both the local and the systemic immune response and is implicated in the modulation of immunity in both healthy and disease states. Recently, quantitative and qualitative changes in the composition of the gut microbiota have been detected in Crohn's disease and ulcerative colitis, reinforcing the hypothesis of dysbiosis as a relevant mechanism underlying inflammatory bowel disease (IBD) pathogenesis. Humans and microbes have co-existed and co-evolved for a long time in a mutually beneficial symbiotic association essential for maintaining homeostasis...
March 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28403629/methylation-of-slfn11-is-a-marker-of-poor-prognosis-and-cisplatin-resistance-in-colorectal-cancer
#18
Tao He, Meiying Zhang, Ruipan Zheng, Shufang Zheng, Enqiang Linghu, James G Herman, Mingzhou Guo
AIM: The expression of human SLFN11 was reported to sensitize cancer cells to DNA damaging agents. This study is to explore the epigenetic change and the function of SLFN11 in human colorectal cancer (CRC). MATERIALS & METHODS: Six CRC cell lines and 128 primary CRC samples were used. RESULTS: SLFN11 was methylated in 55.47% (71/128) of primary CRC. The expression of SLFN11 was regulated by promoter region methylation. Methylation of SLFN11 was significantly associated with age, poor 5-year overall survival and 5-year relapse-free survival (all p < 0...
April 13, 2017: Epigenomics
https://www.readbyqxmd.com/read/28403538/human-papillomavirus-epstein-barr-virus-and-methylation-status-of-p16-ink4a-in-penile-cancer
#19
L A Afonso, F N Carestiato, A A Ornellas, P Ornellas, W M Rocha, T I Cordeiro, D C Lisboa, G Alves, Smb Cavalcanti
Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16(ink4a) in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16(ink4a) was detected in 64...
April 12, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28401018/otx2-expression-contributes-to-proliferation-and-progression-in-myc-amplified-medulloblastoma
#20
REVIEW
Yining Lu, Collin M Labak, Neha Jain, Ian J Purvis, Maheedhara R Guda, Sarah E Bach, Andrew J Tsung, Swapna Asuthkar, Kiran K Velpula
Medulloblastoma is one of the most prevalent pediatric brain malignancies, accounting for approximately 20% of all primary CNS tumors in children under the age of 19. OTX2 is the member of a highly conserved family of bicoid-like homeodomain transcription factors responsible for the regulation of cerebellar development and of current investigational interest in the tumorigenesis of medulloblastoma. Recent studies have revealed that Group 3 and Group 4 medulloblastomas show marked overexpression of OTX2 with a concurrent amplification of the MYC and MYCN oncogenes, respectively, correlating with anaplasticity and unfavorable patient outcomes...
2017: American Journal of Cancer Research
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