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Epigenetic and aging

Mariella G Filbin, Dominik Sturm
Gliomas are the most common primary central nervous system (CNS) neoplasms in children and adolescents and are thought to arise from their glial progenitors or stem cells. Although the exact cells of origin for most pediatric gliomas remain to be identified, our current understanding is that specific cell populations during CNS development are susceptible to particular oncogenic events during certain time windows and thus give rise to pediatric gliomas with distinct histological, molecular, and clinical features...
February 2018: Seminars in Neurology
Rebecca C Richmond, Gemma C Sharp, Georgia Herbert, Charlotte Atkinson, Caroline Taylor, Sohinee Bhattacharya, Doris Campbell, Marion Hall, Nabila Kazmi, Tom Gaunt, Wendy McArdle, Susan Ring, George Davey Smith, Andy Ness, Caroline L Relton
Background: It has been proposed that maternal folic-acid supplement use may alter the DNA-methylation patterns of the offspring during the in-utero period, which could influence development and later-life health outcomes. Evidence from human studies suggests a role for prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood. Methods: To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST-a trial of two different doses: 0...
March 12, 2018: International Journal of Epidemiology
Robert John Aitken
This article is a personal perspective on male infertility, a condition that is not only extremely prevalent but also a major reason for couples to resort to assisted reproductive technology. The introduction of intra-cytoplasmic sperm injection (ICSI) as a form of facilitated fertilization had a revolutionary impact on our capacity to treat cases of male infertility associated with severely-compromised semen quality. However, the widespread use of this technique is also thought to pose risks in terms of the incidence of miscarriage, the health and wellbeing of the offspring and perpetuation of the infertile phenotype into future generations...
March 13, 2018: Molecular Human Reproduction
Yun Hu, Qinwei Sun, Yan Hu, Zhen Hou, Yibo Zong, Nagmeldin A Omer, Halima Abobaker, Ruqian Zhao
Background: We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. Objective: In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms...
March 1, 2018: Journal of Nutrition
Haiyan Qin, Guang Zhang, Lianbo Zhang
Polycomb group genes (PcG) encode chromatin modification proteins that are involved in the epigenetic regulation of cell differentiation, proliferation and the aging processes. The key subunit of the PcG complex, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), has a central role in a variety of mechanisms, such as the formation of chromatin structure, gene expression regulation and DNA damage. In the present study, ultraviolet A (UVA) was used to radiate human dermal fibroblasts in order to construct a photo-aged cell model...
April 2018: Experimental and Therapeutic Medicine
Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Ximena Corso-Díaz, Catherine Jaeger, Vijender Chaitankar, Anand Swaroop
Complex biological processes, such as organogenesis and homeostasis, are stringently regulated by genetic programs that are fine-tuned by epigenetic factors to establish cell fates and/or to respond to the microenvironment. Gene regulatory networks that guide cell differentiation and function are modulated and stabilized by modifications to DNA, RNA and proteins. In this review, we focus on two key epigenetic changes - DNA methylation and histone modifications - and discuss their contribution to retinal development, aging and disease, especially in the context of age-related macular degeneration (AMD) and diabetic retinopathy...
March 12, 2018: Progress in Retinal and Eye Research
Tinashe Mutize, Zibusiso Mkandla, Bongani B Nkambule
BACKGROUND: DNA methylation (global and gene-specific) has been reported as an epigenetic mechanism that could be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Furthermore, epigenetic therapy has been suggested as a future possibility for T2DM treatment. Epigenetic changes illustrate the environmental link of the disease. Since some of the epigenetic modifications can be reversed, they could be used as potential therapeutic targets. The aim of the systematic review will be to synthesise the available evidence pertaining to the link between DNA methylation and T2DM...
March 15, 2018: Systematic Reviews
Núria Folguera-Blasco, Elisabet Cuyàs, Javier A Menéndez, Tomás Alarcón
Understanding the control of epigenetic regulation is key to explain and modify the aging process. Because histone-modifying enzymes are sensitive to shifts in availability of cofactors (e.g. metabolites), cellular epigenetic states may be tied to changing conditions associated with cofactor variability. The aim of this study is to analyse the relationships between cofactor fluctuations, epigenetic landscapes, and cell state transitions. Using Approximate Bayesian Computation, we generate an ensemble of epigenetic regulation (ER) systems whose heterogeneity reflects variability in cofactor pools used by histone modifiers...
March 15, 2018: PLoS Computational Biology
Weizhi Yu, Hong Xu, Ying Xue, Dong An, Huairui Li, Wei Chen, Deqin Yu, Yiping Sun, Jianmei Ma, Yiyuan Tang, Zhaoyang Xiao, Shengming Yin
Introduction: Social isolation enhances the aggressive behavior of animals, but the detailed mechanism remains unclear. Epigenetic studies have suggested that Htr2c RNA editing is closely related to aggressive behavior. This study aims to obtain a fundamental understanding of how social isolation impacts adenosine deaminase acting on RNA 1 (ADAR1, RNA editing enzyme) and Htr2c RNA editing, leading to aggressive behavior, and explore the effective solutions for the recovery of this behavior...
March 2018: Brain and Behavior
Warren Winick-Ng, R Jane Rylett
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons...
2018: Frontiers in Molecular Neuroscience
Sun-Ju Yi, Kyunghwan Kim
Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation...
March 15, 2018: BMB Reports
Adam J Krieg, Sarah R Mullinax, Frances Grimstad, Kaitlin Marquis, Elizabeth Constance, Yan Hong, Sacha A Krieg, Katherine F Roby
PURPOSE: To assess expression of the histone demethylases KDM4A and KDM4B in granulosa collected from women undergoing oocyte retrieval and to determine if expression was related to pregnancy outcome. METHODS: Cumulus and mural granulosa cells were obtained from women undergoing oocyte retrieval. KDM4A and KDM4B mRNA expression was determined by qRT-PCR. KDM4A and KDM4B proteins were immunohistochemically localized in ovarian tissue sections obtained from archival specimens...
March 14, 2018: Journal of Assisted Reproduction and Genetics
Louise Rasmussen, Ib Jarle Christensen, Marielle Herzog, Jake Micallef, Hans Jørgen Nielsen
The aim was to evaluate serum levels of circulating cell-free nucleosomes (ccfn) containing a variety of epigenetic signals including 5-methylcytosine DNA, histone modifications H3K9Me3, H3K9Ac, H3S10PO4, H3K36Me3, H4K20Me3, H4PanAc and pH2AX, nucleosome variant H2AZ and nucleosome adducts with HMGB1 and EZH2 as well as ccfn per se, in addition to develop and evaluate predictor models based on the above mentioned ccfn and including serum levels of carcinoembryonic antigen (CEA), in early detection of colorectal cancer (CRC)...
February 13, 2018: Oncotarget
Cilia Mejia-Lancheros, John Mehegan, Celine M Murrin, Cecily C Kelleher
BACKGROUND/OBJECTIVES: The role of smoking from the paternal line during the pre-conception period on grand-child's overweight/obesity and associated underlying pathways are uncertain. We examined whether the smoking status from the paternal line was associated with the grand-child's higher weight at birth, and overweight or obesity at 5 and 9 years of age. The grandparental smoking effect from the maternal line was also explored. SUBJECTS/METHODS: Participants were fathers and grandparents and grand-children from the Lifeways Cross Generational Cohort (N = 1021 for the analysis at birth; N = 562 and N = 284 for the analysis at 5 and 9 years, respectively)...
March 13, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Simone Accordini, Lucia Calciano, Ane Johannessen, Laura Portas, Bryndis Benediktsdóttir, Randi Jacobsen Bertelsen, Lennart Bråbäck, Anne-Elie Carsin, Shyamali C Dharmage, Julia Dratva, Bertil Forsberg, Francisco Gomez Real, Joachim Heinrich, John W Holloway, Mathias Holm, Christer Janson, Rain Jögi, Bénédicte Leynaert, Andrei Malinovschi, Alessandro Marcon, Jesús Martínez-Moratalla Rovira, Chantal Raherison, José Luis Sánchez-Ramos, Vivi Schlünssen, Roberto Bono, Angelo G Corsico, Pascal Demoly, Sandra Dorado Arenas, Dennis Nowak, Isabelle Pin, Joost Weyler, Deborah Jarvis, Cecilie Svanes
Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not...
March 9, 2018: International Journal of Epidemiology
Zhi-Jie Wu, Xin Zhao, Lauren G Banaszak, Fernanda Gutierrez-Rodrigues, Keyvan Keyvanfar, Shou-Guo Gao, Diego Quinones Raffo, Sachiko Kajigaya, Neal S Young
Additional sex combs-like 1 (ASXL1) is a well‑known tumor suppressor gene and epigenetic modifier. ASXL1 mutations are frequent in myeloid malignances; these mutations are risk factors for the development of myelodysplasia and also appear as small clones during normal aging. ASXL1 appears to act as an epigenetic regulator of cell survival and myeloid differentiation; however, the molecular mechanisms underlying the malignant transformation of cells with ASXL1 mutations are not well defined. Using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) genome editing, heterozygous and homozygous ASXL1 mutations were introduced into human U937 leukemic cells...
April 2018: International Journal of Oncology
Rosita Gabbianelli, Elisabetta Damiani
Neurodegeneration represents a global problem due to the progressive increase in the aging population all over the world. The quality of life in aging and the cost for the health care system require actions to promote healthy aging. In this regard, several risk factors associated with the development of neurodegeneration can be identified, and programs to educate people on the key role of prevention could significantly ameliorate the future picture of the aging population. Here we describe the key role of the pre- and postnatal period of life during the first 1000 days of life, focusing on the importance of nutrition and a healthy lifestyle of mother and offspring for the prevention of neurodegeneration later in life...
February 9, 2018: Journal of Nutritional Biochemistry
Hemant Gujar, Jane W Liang, Nicholas C Wong, Khyobeni Mozhui
The Illumina Infinium MethylationEPIC provides an efficient platform for profiling DNA methylation in humans at over 850,000 CpGs. Model organisms such as mice do not currently benefit from an equivalent array. Here we used this array to measure DNA methylation in mice. We defined probes targeting conserved regions and performed differential methylation analysis and compared between the array-based assay and affinity-based DNA sequencing of methyl-CpGs (MBD-seq) and reduced representation bisulfite sequencing...
2018: PloS One
Alexander N Yatsenko, Paul J Turek
PURPOSE: To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring. METHODS: Review of published PubMed literature. RESULTS: Advanced paternal age (> 40 years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10)...
March 9, 2018: Journal of Assisted Reproduction and Genetics
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