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Epigenetic Age

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https://www.readbyqxmd.com/read/29913211/nrf2-molecular-and-epigenetic-regulation-during-aging
#1
REVIEW
A Silva-Palacios, M Ostolga-Chavarría, C Zazueta, M Königsberg
Increase in life-span is commonly related with age-related diseases and with gradual loss of genomic, proteomic and metabolic integrity. Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) controls the expression of genes whose products include antioxidant proteins, detoxifying enzymes, drug transporters and numerous cytoprotective proteins. Several experimental approaches have evaluated the potential regulation of the transcription factor Nrf2 to enhance the expression of genes that contend against accumulative oxidative stress and promote healthy aging...
June 15, 2018: Ageing Research Reviews
https://www.readbyqxmd.com/read/29912901/germline-mutations-and-somatic-inactivation-of-trim28-in-wilms-tumour
#2
Benjamin J Halliday, Ryuji Fukuzawa, David M Markie, Richard G Grundy, Jackie L Ludgate, Michael A Black, Jane E Skeen, Robert J Weeks, Daniel R Catchpoole, Aedan G K Roberts, Anthony E Reeve, Ian M Morison
Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing...
June 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29912290/accounting-for-differential-variability-in-detecting-differentially-methylated-regions
#3
Ya Wang, Andrew E Teschendorff, Martin Widschwendter, Shuang Wang
DNA methylation plays an essential role in cancer. Differential variability (DV) in cancer was recently observed that contributes to cancer heterogeneity and has been shown to be crucial in detecting epigenetic field defects, DNA methylation alterations happening early in carcinogenesis. As neighboring CpG sites are highly correlated, here, we present a new method to detect differentially methylated regions (DMRs) that uses combined signals from differential methylation and DV between sample groups. We demonstrated in simulation studies the superior performance of the new method than existing methods that use only one type of signals when true DMRs have both...
August 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29906262/exposure-to-polycyclic-aromatic-hydrocarbons-and-accelerated-dna-methylation-aging
#4
Jun Li, Xiaoyan Zhu, Kuai Yu, Haijing Jiang, Yizhi Zhang, Biqi Wang, Xuezhen Liu, Siyun Deng, Jie Hu, Qifei Deng, Huizhen Sun, Huan Guo, Xiaomin Zhang, Weihong Chen, Jing Yuan, Meian He, Yansen Bai, Xu Han, Bing Liu, Chuanyao Liu, Yanjun Guo, Bing Zhang, Zhihong Zhang, Frank B Hu, Wenjing Gao, Liming Li, Mark Lathrop, Catherine Laprise, Liming Liang, Tangchun Wu
BACKGROUND: Aging is related to an increased risk of morbidity and mortality and is affected by environmental factors. Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse health outcomes; but the association of such exposure with DNA methylation aging, a novel aging marker, is unclear. OBJECTIVES: Our aim was to investigate the association of PAH exposure with methylation aging. METHODS: We trained and validated a methylation age predictor suitable for Chinese populations using whole blood methylation data in 989 Chinese and 160 Caucasians...
June 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29901700/epigenomics-and-metabolomics-reveal-the-mechanism-of-the-apoa2-saturated-fat-intake-interaction-affecting-obesity
#5
Chao-Qiang Lai, Caren E Smith, Laurence D Parnell, Yu-Chi Lee, Dolores Corella, Paul Hopkins, Bertha A Hidalgo, Stella Aslibekyan, Michael A Province, Devin Absher, Donna K Arnett, Katherine L Tucker, Jose M Ordovas
Background: The putative functional variant -265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity. Objective: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction. Design: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (<22 g/d) or high-SFA diet (≥22 g/d), matched for age, sex, BMI, and diabetes status in the Boston Puerto Rican Health Study (BPRHS)...
June 12, 2018: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/29898284/a-within-subject-consideration-of-the-psychotic-spectrum-disorder-concept-in-a-patient-in-remission-associated-with-cortical-gray-matter-recovery
#6
Herbert Y Meltzer, Min Young Sim, Adam Anderson, Christopher Cannistraci, Karu Jayathilake, Daniel Barrett Share, Myung Lee
INTRODUCTION: Psychotic spectrum disorder (PSD) links the syndromes of bipolar disorder, psychotic depression, and schizophrenia, often viewed as unique disorders. AIMS: Application of the PSD concept to a single patient rather than across groups of patients and demonstration of a remarkable remission of schizophrenia phenotype with recovery of gray matter in specific brain regions. RESULTS: We report a woman who experienced discrete, nonoverlapping periods of each of the above syndromes, in the order noted, over a 30-year period, followed by abrupt ending of psychosis and full remission lasting at least 7 years...
July 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29898036/role-of-non-coding-rnas-in-non-aging-related-neurological-disorders
#7
A S Vieira, D B Dogini, I Lopes-Cendes
Protein coding sequences represent only 2% of the human genome. Recent advances have demonstrated that a significant portion of the genome is actively transcribed as non-coding RNA molecules. These non-coding RNAs are emerging as key players in the regulation of biological processes, and act as "fine-tuners" of gene expression. Neurological disorders are caused by a wide range of genetic mutations, epigenetic and environmental factors, and the exact pathophysiology of many of these conditions is still unknown...
June 11, 2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29897034/posttraumatic-psychopathology-and-the-pace-of-the-epigenetic-clock-a-longitudinal-investigation
#8
Erika J Wolf, Mark W Logue, Filomene G Morrison, Elizabeth S Wilcox, Annjanette Stone, Steven A Schichman, Regina E McGlinchey, William P Milberg, Mark W Miller
BACKGROUND: Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i...
June 13, 2018: Psychological Medicine
https://www.readbyqxmd.com/read/29895819/genome-wide-association-study-in-japanese-females-identifies-fifteen-novel-skin-related-trait-associations
#9
Chihiro Endo, Todd A Johnson, Ryoko Morino, Kazuyuki Nakazono, Shigeo Kamitsuji, Masanori Akita, Maiko Kawajiri, Tatsuya Yamasaki, Azusa Kami, Yuria Hoshi, Asami Tada, Kenichi Ishikawa, Maaya Hine, Miki Kobayashi, Nami Kurume, Yuichiro Tsunemi, Naoyuki Kamatani, Makoto Kawashima
Skin trait variation impacts quality-of-life, especially for females from the viewpoint of beauty. To investigate genetic variation related to these traits, we conducted a GWAS of various skin phenotypes in 11,311 Japanese women and identified associations for age-spots, freckles, double eyelids, straight/curly hair, eyebrow thickness, hairiness, and sweating. In silico annotation with RoadMap Epigenomics epigenetic state maps and colocalization analysis of GWAS and GTEx Project eQTL signals provided information about tissue specificity, candidate causal variants, and functional target genes...
June 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29895583/dna-methylation-of-telomere-related-genes-and-cancer-risk
#10
Brian Thomas Joyce, Yinan Zheng, Drew Nannini, Zhou Zhang, Lei Liu, Tao Gao, Masha Kocherginsky, Robert Murphy, Hushan Yang, Chad J Achenbach, Lewis R Roberts, Mirjam Hoxha, Jincheng Shen, Pantel Vokonas, Joel Schwartz, Andrea Baccarelli, Lifang Hou
Researchers hypothesized that telomere shortening facilitates carcinogenesis. Previous studies found inconsistent associations between blood leukocyte telomere length (LTL) and cancer. Epigenetic reprogramming of telomere maintenance mechanisms may help explain this inconsistency. We examined associations between DNA methylation in telomere-related genes (TRGs) and cancer. We analyzed 475 participants providing 889 samples 1-3 times (median follow up: 10.1 years) from 1999-2013 in the Normative Aging Study...
June 12, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29893918/tissue-specific-dna-methylation-loss-during-ageing-and-carcinogenesis-is-linked-to-chromosome-structure-replication-timing-and-cell-division-rates
#11
Marija Dmitrijeva, Stephan Ossowski, Luis Serrano, Martin H Schaefer
DNA methylation is an epigenetic mechanism known to affect gene expression and aberrant DNA methylation patterns have been described in cancer. However, only a small fraction of differential methylation events target genes with a defined role in cancer, raising the question of how aberrant DNA methylation contributes to carcinogenesis. As recently a link has been suggested between methylation patterns arising in ageing and those arising in cancer, we asked which aberrations are unique to cancer and which are the product of normal ageing processes...
June 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29892055/brain-age-and-other-bodily-ages-implications-for-neuropsychiatry
#12
REVIEW
James H Cole, Riccardo E Marioni, Sarah E Harris, Ian J Deary
As our brains age, we tend to experience cognitive decline and are at greater risk of neurodegenerative disease and dementia. Symptoms of chronic neuropsychiatric diseases are also exacerbated during ageing. However, the ageing process does not affect people uniformly; nor, in fact, does the ageing process appear to be uniform even within an individual. Here, we outline recent neuroimaging research into brain ageing and the use of other bodily ageing biomarkers, including telomere length, the epigenetic clock, and grip strength...
June 11, 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29891535/aged-murine-hematopoietic-stem-cells-drive-aging-associated-immune-remodeling
#13
Hanna Leins, Medhanie Mulaw, Karina Eiwen, Vadim Sakk, Ying Liang, Michael Denkinger, Hartmut Geiger, Reinhold Schirmbeck
Aging-associated remodeling of the immune system impairs its functional integrity and contributes to increased morbidity and mortality in the elderly. Aging of hematopoietic stem cells (HSCs), from which all cells of the adaptive immune system ultimately originate, might play a crucial role in the remodeling of the aged immune system. We recently reported that aging of HSCs is, in part, driven by elevated activity of the small RhoGTPase Cdc42 and that aged HSCs can be rejuvenated in vitro by inhibition of the elevated Cdc42 activity in aged HSCs with the pharmacological compound CASIN...
June 11, 2018: Blood
https://www.readbyqxmd.com/read/29889250/prevalence-and-molecular-characteristics-of-defective-mismatch-repair-epithelial-ovarian-cancer-in-a-japanese-hospital-based-population
#14
Yusuke Tajima, Hidetaka Eguchi, Noriyasu Chika, Tomonori Nagai, Sariya Dechamethakun, Kensuke Kumamoto, Tetsuhiko Tachikawa, Kiwamu Akagi, Jun-Ichi Tamaru, Hiroyuki Seki, Yasushi Okazaki, Hideyuki Ishida
Background: The prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancers in the Japanese population have scarcely been investigated. Methods: Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary epithelial ovarian cancers in patients who underwent oophorectomy at our institution between April 2005 and September 2014...
June 8, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29888314/reduced-left-ventricular-dimension-and-function-following-early-life-stress-a-thrifty-phenotype-hypothesis-engendering-risk-for-mood-and-anxiety-disorders
#15
Jeremy D Coplan, Anna V Rozenboym, Sasha L Fulton, Venkatesh Panthangi, Jean Tang, Lakshmi Thiramangalakdi, Tarique D Perera, Yang Liu, Haroon Kamran, Michael J Owens, Charles B Nemeroff, Leonard A Rosenblum, John G Kral, Louis Salciccioli, Jason Lazar
Background: Early life stress (ELS) in macaques in the form of insecure maternal attachment putatively induces epigenetic adaptations resulting in a "thrifty phenotype" throughout the life cycle. For instance, ELS induces persistent increases in insulin resistance, hippocampal and corpus callosum atrophy and reduced "behavioral plasticity", which, taken together, engenders an increased risk for mood and anxiety disorders in humans but also a putative sparing of calories...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29888306/accelerated-dna-methylation-aging-and-increased-resilience-in-veterans-the-biological-cost-for-soldiering-on
#16
Divya Mehta, Dagmar Bruenig, Bruce Lawford, Wendy Harvey, Tania Carrillo-Roa, Charles P Morris, Tanja Jovanovic, Ross McD Young, Elisabeth B Binder, Joanne Voisey
Accelerated epigenetic aging, the difference between the DNA methylation-predicted age (DNAm age) and the chronological age, is associated with a myriad of diseases. This study investigates the relationship between epigenetic aging and risk and protective factors of PTSD. Genome-wide DNA methylation analysis was performed in 211 individuals including combat-exposed Australian veterans (discovery cohort, n = 96 males) and trauma-exposed civilian males from the Grady Trauma Project (replication cohort, n = 115 males)...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29887832/aging-hallmarks-the-benefits-of-physical-exercise
#17
REVIEW
Alexandre Rebelo-Marques, Adriana De Sousa Lages, Renato Andrade, Carlos Fontes Ribeiro, Anabela Mota-Pinto, Francisco Carrilho, João Espregueira-Mendes
World population has been continuously increasing and progressively aging. Aging is characterized by a complex and intraindividual process associated with nine major cellular and molecular hallmarks, namely, genomic instability, telomere attrition, epigenetic alterations, a loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. This review exposes the positive antiaging impact of physical exercise at the cellular level, highlighting its specific role in attenuating the aging effects of each hallmark...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29887568/the-causal-relationship-between-epigenetic-abnormality-and-cancer-development-in-vivo-reprogramming-and-its-future-application
#18
Yosuke Yamada, Yasuhiro Yamada
There is increasing evidence that cancer cells acquire epigenetic abnormalities as well as genetic mutations during cancer initiation, maintenance, and progression. However, the role of epigenetic regulation in cancer development, especially at the organismal level, remains to be elucidated. Here, we describe the causative role of epigenetic abnormalities in cancer, referring to our in vivo studies using induced pluripotent stem cell technology. We first summarize epigenetic reorganization during cellular reprogramming and introduce our in vivo reprogramming system for investigating the impact of dedifferentiation-driven epigenetic disruption in cancer development...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29885742/epigenetic-regulation-in-neurodegenerative-diseases
#19
REVIEW
Amit Berson, Raffaella Nativio, Shelley L Berger, Nancy M Bonini
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS)...
June 6, 2018: Trends in Neurosciences
https://www.readbyqxmd.com/read/29884649/impaired-dna-demethylation-of-c-ebp-sites-causes-premature-aging
#20
Andrea Schäfer, Bernadette Mekker, Medhavi Mallick, Viviana Vastolo, Emil Karaulanov, Dominik Sebastian, Carina von der Lippen, Bernd Epe, Damien J Downes, Carola Scholz, Christof Niehrs
Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp ( CCAAT/enhancer-binding protein ) mutants...
June 8, 2018: Genes & Development
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