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Epigenetics and aging

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https://www.readbyqxmd.com/read/28526334/regulatory-cis-and-trans-elements-of-mitochondrial-d-loop-driven-reporter-genes-in-budding-tunicates
#1
Kaz Kawamura, Yuhya Saitoh, Loriano Ballarin, Takeshi Sunanaga
To unveil the underlying mechanism of mitochondrial gene regulation associated with ageing and budding in the tunicate Polyandrocarpa misakiensis, mitochondrial non-coding-region (NCR)-containing reporter genes were constructed. PmNCR2.3K/GFP was expressed spatiotemporally in a pattern quite similar to mitochondrial 16SrRNA. The reporter gene expression was sensitive to high dose of rifampicin similar to mitochondrial genes, suggesting that the transcription indeed occurs in mitochondria. However, the gene expression also occurred in vivo in the cell nucleus and in vitro in the nuclear extracts...
May 16, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28523554/alzheimer-s-disease-and-histone-code-alterations
#2
Pritika Narayan, Mike Dragunow
Substantial progress has been made in identifying Alzheimer's disease (AD) risk-associated variants using genome-wide association studies (GWAS). The majority of these risk variants reside in noncoding regions of the genome making their functional evaluation difficult; however, they also infer the presence of unconventional regulatory regions that may reside at these locations. We know from these studies that rare familial cases of AD account for less than 5% of all AD cases and autosomal dominant mutations in APP, PSEN1 and PSEN2 account for less than 10% of the genetic basis of these familial cases [1]...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523553/dna-modifications-and-alzheimer-s-disease
#3
Rebecca G Smith, Katie Lunnon
Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide. While a number of studies have focused on identifying genetic variants that contribute to the development and progression of late-onset AD, the majority of these only have a relatively small effect size. There are also a number of other risk factors, for example, age, gender, and other comorbidities; however, how these influence disease risk is not known. Therefore, in recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523547/dna-methylation-in-major-depressive-disorder
#4
Ehsan Pishva, Bart P F Rutten, Daniel van den Hove
Epigenetic mechanisms regulate gene expression, influencing protein levels and ultimately shaping phenotypes during life. However, both stochastic epigenetic variations and environmental reprogramming of the epigenome might influence neurodevelopment and ageing, and this may contribute to the origins of mental ill-health. Studying the role of epigenetic mechanisms is challenging, as genotype-, tissue- and cell type-dependent epigenetic changes have to be taken into account, while the nature of mental disorders also poses significant challenges for linking them with biological profiles...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28523359/arginine-cga-codons-as-a-source-of-nonsense-mutations-a-possible-role-in-multivariant-gene-expression-control-of-mrna-quality-and-aging
#5
Georgy A Romanov, Victor S Sukhoverov
Methylation of cytosine residues in DNA of higher eukaryotes, including humans, creates "hot spots" of C→T transitions in the genome. The predominantly methylated sequence in mammalian DNAs is CG (CpG). Among CG-containing codons, CGA codons for arginine are unique due to their ability to create stop codons TGA (UGA in mRNA) upon epigenetic-mediated mutation. As such nonsense mutations can have a strong adverse effect on the cell and organism, we have performed a study, on the example of human genes, aimed to characterise the anticipated effects of epigenetic-mediated nonsense mutations CGA→TGA in somatic cells...
May 18, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28516910/genetic-architecture-of-epigenetic-and-neuronal-ageing-rates-in-human-brain-regions
#6
Ake T Lu, Eilis Hannon, Morgan E Levine, Eileen M Crimmins, Katie Lunnon, Jonathan Mill, Daniel H Geschwind, Steve Horvath
Identifying genes regulating the pace of epigenetic ageing represents a new frontier in genome-wide association studies (GWASs). Here using 1,796 brain samples from 1,163 individuals, we carry out a GWAS of two DNA methylation-based biomarkers of brain age: the epigenetic ageing rate and estimated proportion of neurons. Locus 17q11.2 is significantly associated (P=4.5 × 10(-9)) with the ageing rate across five brain regions and harbours a cis-expression quantitative trait locus for EFCAB5 (P=3.4 × 10(-20))...
May 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515797/circulating-nucleosomes-as-new-blood-based-biomarkers-for-detection-of-colorectal-cancer
#7
Jean-François Rahier, Anne Druez, Laurence Faugeras, Jean-Paul Martinet, Myriam Géhénot, Eléonore Josseaux, Marielle Herzog, Jake Micallef, Fabienne George, Monique Delos, Thierry De Ronde, Abdenor Badaoui, Lionel D'Hondt
BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic procedure. For this reason, alternative screening tests, in particular, fecal occult blood-based tests, have been widely adopted for frontline screening...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28514935/mesenchymal-stem-cell-based-cartilage-regeneration-approach-and-cell-senescence-can-we-manipulate-cell-aging-and-function
#8
Marta Anna Szychlinska, Martin James Stoddart, Ugo D'Amora, Luigi Ambrosio, Mauro Alini, Giuseppe Musumeci
Aging is the most prominent risk factor triggering several degenerative diseases, such as Osteoarthritis (OA). Due to its poor self-healing capacity, once injured cartilage needs to be re-established. This process mighmight be approached bythrough resorting to cell-based therapies and/or tissue engineering. Human mesenchymal stem cells (hMSC) represent a promising approach due to their chondrogenic differentiation potential. Presently, in vitro chondrogenic differentiation of MSCs is limited by two main reasons: Aging aging of MSCs, which determines the loss of cell proliferative and differentiationed capacity and MSC-derived chondrocyte hypertrophic differentiation, which limits the use of these cells in cartilage tissue regeneration approach...
May 17, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28505433/do-environmental-fluoride-exposure-and-esr%C3%AE-genetic-variation-modulate-methylation-modification-on-bone-changes-in-chinese-farmers
#9
Yanli Zhang, Hui Huang, Biao Gong, Leizhen Duan, Long Sun, Tongkun He, Xuemin Cheng, Zhiyuan Li, Liuxin Cui, Yue Ba
Although increasing evidences suggest that estrogen receptor α (ESRα) genetic variation could modify bone damages caused by environmental fluoride exposure, little is known about epigenetic mechanisms in relation to bone changes. A case-control study was conducted among farmers aged 18-55 years in Henan Province, China. X-ray was used to detect bone changes. Methylation status was determined by methylation-specific PCR. Genotypes were identified by Taqman probe and Real-Time PCR. In this study, we found that methylation status in the promoter region of the ESRα gene was lower in bone change cases than that in controls, which was only observed in male farmers after stratification by gender...
May 15, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28503212/associations-between-maternal-risk-factors-of-adverse-pregnancy-and-birth-outcomes-and-the-offspring-epigenetic-clock-of-gestational-age-at-birth
#10
Polina Girchenko, Jari Lahti, Darina Czamara, Anna K Knight, Meaghan J Jones, Anna Suarez, Esa Hämäläinen, Eero Kajantie, Hannele Laivuori, Pia M Villa, Rebecca M Reynolds, Michael S Kobor, Alicia K Smith, Elisabeth B Binder, Katri Räikkönen
BACKGROUND: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28502862/11-beta-hydroxysteroid-dehydrogenase-2-promoter-methylation-is-associated-with-placental-protein-expression-in-small-for-gestational-age-newborns
#11
Maria-Luisa Lazo-de-la-Vega-Monroy, Martha-Olivia Solís-Martínez, Gustavo Romero-Gutiérrez, Victor E Aguirre-Arzola, Katarzyna Wrobel, Kazimierz Wrobel, Silvio Zaina, Gloria Barbosa-Sabanero
Small for gestational age infants have greater risk of developing metabolic diseases in adult life. It has been suggested that low birth weight may result from glucocorticoid excess in utero, a key mechanism in fetal programming. The placental enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11β-HSD2, HSD11B2 gene) acts as a barrier protecting the fetus from maternal corticosteroid deleterious effects. Low placental 11β-HSD2 transcription and activity have been associated with low birth weight, yet the mechanism regulating its protein expression is not fully understood...
May 11, 2017: Steroids
https://www.readbyqxmd.com/read/28501566/dna-methylation-regulated-gene-expression-in-organ-fibrosis
#12
REVIEW
Xiangyu Zhang, Min Hu, Xing Lyu, Chun Li, Victor J Thannickal, Yan Y Sanders
DNA methylation is a major epigenetic mechanism to regulate gene expression. Epigenetic regulation, including DNA methylation, histone modifications and RNA interference, results in heritable changes in gene expression independent of alterations in DNA sequence. Epigenetic regulation often occurs in response to aging and environment stimuli, including exposures and diet. Studies have shown that DNA methylation is critical in the pathogenesis of fibrosis involving multiple organs sytems, contributing to significant morbidity and mortality...
May 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28500085/the-most-common-vices-of-men-can-damage-fertility-and-the-health-of-the-next-generation
#13
Tod Fullston, Nicole O McPherson, Deirdre Zander-Fox, Michelle Lane
There is growing evidence from animal and human studies that demonstrate that acquired paternal traits can impair both a male's fertility and the health of his offspring, including advanced age, smoking, stress, trauma, under-nutrition, infection, toxin exposure, and obesity. Curiously, many of these factors manifest as impaired neurological, behavioural, and/or metabolic functioning in offspring. The underlying molecular mechanisms that respond to the paternal environment and act as vectors of intergenerational transmission are beginning to emerge...
May 12, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28499883/the-role-of-5-hydroxymethylcytosine-in-development-aging-and-age-related-diseases
#14
REVIEW
V López, A F Fernández, M F Fraga
DNA methylation at the fifth position of cytosines (5mC) represents a major epigenetic modification in mammals. The recent discovery of 5-hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our view of the epigenome, as multiple studies indicate that 5hmC is not simply an intermediate of DNA demethylation, but a genuine epigenetic mark that may play an important functional role in gene regulation. Currently, the availability of platforms that discriminates between the presence of 5mC and 5hmC at single-base resolution is starting to shed light on the functions of 5hmC...
May 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28499412/genome-wide-dna-methylation-analysis-reveals-hypomethylation-in-the-low-cpg-promoter-regions-in-lymphoblastoid-cell-lines
#15
Itsuki Taniguchi, Chihiro Iwaya, Keizo Ohnaka, Hiroki Shibata, Ken Yamamoto
BACKGROUND: Epidemiological studies of DNA methylation profiles may uncover the molecular mechanisms through which genetic and environmental factors contribute to the risk of multifactorial diseases. There are two types of commonly used DNA bioresources, peripheral blood cells (PBCs) and EBV-transformed lymphoblastoid cell lines (LCLs), which are available for genetic epidemiological studies. Therefore, to extend our knowledge of the difference in DNA methylation status between LCLs and PBCs is important in human population studies that use these DNA sources to elucidate the epigenetic risks for multifactorial diseases...
May 12, 2017: Human Genomics
https://www.readbyqxmd.com/read/28496034/effect-of-perinatal-exposure-to-bisphenol-a-on-dna-methylation-and-histone-acetylation-in-cerebral-cortex-and-hippocampus-of-postnatal-male-mice
#16
Dhiraj Kumar, Mahendra Kumar Thakur
Bisphenol-A (BPA) is an estrogenic endocrine disruptor mostly used for the production of polycarbonate plastics and epoxy resins. Recently we have reported that perinatal BPA exposure impaired spatial memory through upregulation of synaptic proteins Neurexin1 and Neuroligin3 in male mice. As epigenetic mechanism is a key regulator of memory, we hypothesized that BPA might influence memory through epigenetic regulation of gene expression. Here we provide evidence that perinatal exposure to BPA decreased 5-mC DNA but increased histone H3 acetylation in cerebral cortex and hippocampus of postnatal 3 and 8 weeks male mice...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28494506/minimal-residual-disease-eradication-with-epigenetic-therapy-in-core-binding-factor-acute-myeloid-leukemia
#17
Brittany Knick Ragon, Naval Daver, Guillermo Garcia-Manero, Farhad Ravandi, Jorge Cortes, Tapan Kadia, Betul Oran, Maro Ohanian, Alessandra Ferrajoli, Naveen Pemmaraju, Hagop M Kantarjian, Gautam Borthakur
Recurrent translocations, t(8;21) or inv(16), in core binding factor acute myeloid leukemia (CBF-AML) are amenable to monitoring for minimal residual disease (MRD) with reverse transcriptase polymerase chain reaction (RTPCR). Despite a favorable prognosis, disease relapse remains the single cause of treatment failure in CBF-AML. Fusion products of these translocations recruit epigenetic silencing complexes resulting in hematopoietic maturation arrest. We hypothesized that maintenance therapy with hypomethylating agents (HMA), including decitabine (DAC) and azacitidine (AZA) after induction/consolidation, can be used for MRD elimination to ultimately prolong relapse free survival...
May 11, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28489894/analysis-of-global-dna-methylation-changes-in-primary-human-fibroblasts-in-the-early-phase-following-x-ray-irradiation
#18
Anna Maierhofer, Julia Flunkert, Marcus Dittrich, Tobias Müller, Detlev Schindler, Indrajit Nanda, Thomas Haaf
Epigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences were usually not significant...
2017: PloS One
https://www.readbyqxmd.com/read/28489601/cellular-senescence-senescence-associated-secretory-phenotype-and-chronic-kidney-disease
#19
REVIEW
Wen-Juan Wang, Guang-Yan Cai, Xiang-Mei Chen
Chronic kidney disease (CKD) is increasingly being accepted as a type of renal ageing. The kidney undergoes age-related alterations in both structure and function. To date, a comprehensive analysis of cellular senescence and senescence-associated secretory phenotype (SASP) in CKD is lacking. Hence, this review mainly discusses the relationship between the two phenomena to show the striking similarities between SASP and CKD-associated secretory phenotype (CASP). It has been reported that replicative senescence, stress-induced premature ageing, and epigenetic abnormalities participate in the occurrence and development of CKD...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487351/gestational-high-fat-diet-and-bisphenol-a-exposure-heightens-mammary-cancer-risk
#20
Yuet-Kin Leung, Vinothini Govindarajah, Ana Cheong, Jen Veevers, Dan Song, Robin Gear, Xuegong Zhu, Jun Ying, Ady Kendler, Mario Medvedovic, Scott Belcher, Shuk-Mei Ho
In utero exposure to bisphenol A (BPA) increases mammary cancer susceptibility in offspring. High fat diet is widely believed to be a risk factor of breast cancer. The objective of this study was to determine whether maternal exposure to BPA in addition to high-butterfat (HBF) intake during pregnancy further impacts carcinogen-induced mammary cancer risk in offspring, and its dose-response curve. In this study, we found that gestational HBF intake in addition to a low-dose BPA (25 µg/kg BW/day) exposure increased mammary tumor incidence in a 50-day-of-age chemical carcinogen administration model and altered mammary gland morphology in offspring in a non-monotonic manner, while shortening tumor-free survival time compared with the HBF-alone group...
May 9, 2017: Endocrine-related Cancer
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