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Epigenetics and aging

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https://www.readbyqxmd.com/read/29679395/placental-adaptations-to-micronutrient-dysregulation-in-the-programming-of-chronic-disease
#1
Pierre Hofstee, Daniel McKeating, Anthony V Perkins, James S M Cuffe
Poor nutrition during pregnancy is known to impair foetal development and increase the risk of chronic disease in offspring. Both macronutrients and micronutrients are required for a healthy pregnancy although significantly less is understood about the role of micronutrients in the programming of chronic disease. This is despite the fact that modern calorie rich diets are often also deficient in key micronutrients. The importance of micronutrients in gestational disorders is clearly understood but how they impact long term disease in humans requires further investigation...
April 21, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29676998/an-epigenetic-biomarker-of-aging-for-lifespan-and-healthspan
#2
Morgan E Levine, Ake T Lu, Austin Quach, Brian H Chen, Themistocles L Assimes, Stefania Bandinelli, Lifang Hou, Andrea A Baccarelli, James D Stewart, Yun Li, Eric A Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, Steve Horvath
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease...
April 18, 2018: Aging
https://www.readbyqxmd.com/read/29675884/specific-breast-cancer-prognosis-subtype-distinctions-based-on-dna-methylation-patterns
#3
Shumei Zhang, Yihan Wang, Yue Gu, Jiang Zhu, Ce Ci, Zhongfu Guo, Chuangeng Chen, Yanjun Wei, Wenhua Lv, Hongbo Liu, Dongwei Zhang, Yan Zhang
Tumor heterogeneity is an obstacle to effective breast cancer diagnosis and therapy. DNA methylation is an important regulator of gene expression, thus characterizing tumor heterogeneity by epigenetic features can be clinically informative. In this study, we explored specific prognosis-subtypes based on DNA methylation status using 669 breast cancers from TCGA database. Nine subgroups were distinguished by consensus clustering using 3869 CpGs that significantly influenced survival. The specific DNA methylation patterns were reflected by different races, ages, tumor stages, receptor status, histological types, metastasis status and prognosis...
April 19, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29674182/forensic-epigenetic-age-estimation-and-beyond-ethical-and-legal-considerations
#4
Mahsa Shabani, Pascal Borry, Inge Smeers, Bram Bekaert
Forensic geneticists are in a race to develop methods based on DNA methylation for various forensic applications, including age estimation. We argue that using epigenetic biomarkers could reveal a broad range of health and life-style related information, therefore it is necessary to develop adequate safeguards to protect the privacy of the individuals under scrutiny.
April 16, 2018: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29671387/positioning-europe-for-the-epitranscriptomics-challenge
#5
Michael Jantsch, Alessandro Quattrone, Mary O'Connell, Mark Helm, Michaela Frye, Manuel Macias-Gonzales, Marie Ohman, Stefan Ameres, Luc Willems, Francois Fuks, Anastasis Oulas, Stepanka Vanacova, Henrik Nielsen, Cecile Bousquet-Antonelli, Yuri Motorin, Jean-Yves Roignant, Nikolaos Balatsos, Andras Dinnyes, Pavel Baranov, Vincent Kelly, Ayelet Lamm, Gideon Rechavi, Mattia Pelizzola, Janis Liepins, Irina Holodnuka Kholodnyuk, Vanessa Zammit, Duncan Ayers, Finn Drablos, John Arne Dahl, Janusz Bujnicki, Carmen Jeronimo, Raquel Almeida, Monica Neagu, Marieta Costache, Jasna Bankovic, Bojana Banovic, Jan Kyselovic, Luis Miguel Valor, Stefan Selbert, Pinar Pir, Turan Demircan, Victoria Cowling, Matthias Schäfer, Walter Rossmanith, Denis Lafontaine, Alexandre David, Clement Carre, Frank Lyko, Raffael Schaffrath, Schraga Schwartz, Andre Verdel, Arne Klungland, Elzbieta Purta, Gordana Timotijevic, Fernando Cardona, Alberto Davalos, Ester Ballana, Donal O Carroll, Jernej Ule, Rupert Fray
The genetic alphabet consists of the four letters: C, A, G, and T in DNA and C,A,G, and U in RNA. Triplets of these four letters jointly encode 20 different amino acids out of which proteins of all organisms are built. This system is universal and is found in all kingdoms of life. However, bases in DNA and RNA can be chemically modified. In DNA, around 10 different modifications are known, and those have been studied intensively over the past 20 years. Scientific studies on DNA modifications and proteins that recognize them gave rise to the large field of epigenetic and epigenomic research...
April 19, 2018: RNA Biology
https://www.readbyqxmd.com/read/29670212/mitochondrial-dna-variation-and-the-pathogenesis-of-osteoarthritis-phenotypes
#6
REVIEW
Francisco J Blanco, Ana M Valdes, Ignacio Rego-Pérez
Mitochondria and mitochondrial DNA (mtDNA) variation are now recognized as important factors in the development of osteoarthritis (OA). Mitochondria are the energy powerhouses of the cell, and also regulate different processes involved in the pathogenesis of OA including inflammation, apoptosis, calcium metabolism and the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Mitochondria contain their own genetic material, mtDNA, which evolved through the sequential accumulation of mtDNA variants to enable humans to adapt to different climates...
April 18, 2018: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/29670042/long-non-coding-rnas-in-neuronal-aging
#7
REVIEW
Diana Pereira Fernandes, Mainá Bitar, Frank M J Jacobs, Guy Barry
The expansion of long non-coding RNAs (lncRNAs) in organismal genomes has been associated with the emergence of sophisticated regulatory networks that may have contributed to more complex neuronal processes, such as higher-order cognition. In line with the important roles of lncRNAs in the normal functioning of the human brain, dysregulation of lncRNA expression has been implicated in aging and age-related neurodegenerative disorders. In this paper, we discuss the function and expression of known neuronal-associated lncRNAs, their impact on epigenetic changes, the contribution of transposable elements to lncRNA expression, and the implication of lncRNAs in maintaining the 3D nuclear architecture in neurons...
April 18, 2018: Non-Coding RNA
https://www.readbyqxmd.com/read/29669575/effects-of-senolytic-drugs-on-human-mesenchymal-stromal-cells
#8
Clara Grezella, Eduardo Fernandez-Rebollo, Julia Franzen, Mónica Sofia Ventura Ferreira, Fabian Beier, Wolfgang Wagner
BACKGROUND: Senolytic drugs are thought to target senescent cells and might thereby rejuvenate tissues. In fact, such compounds were suggested to increase health and lifespan in various murine aging models. So far, effects of senolytic drugs have not been analysed during replicative senescence of human mesenchymal stromal cells (MSCs). METHODS: In this study, we tested four potentially senolytic drugs: ABT-263 (navitoclax), quercetin, nicotinamide riboside, and danazol...
April 18, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29666616/stem-cell-transcription-factor-foxo-controls-microbiome-resilience-in-hydra
#9
Benedikt M Mortzfeld, Jan Taubenheim, Sebastian Fraune, Alexander V Klimovich, Thomas C G Bosch
The aging process is considered to be the result of accumulating cellular deterioration in an individual organism over time. It can be affected by the combined influence of genetic, epigenetic, and environmental factors including life-style-associated events. In the non-senescent freshwater polyp Hydra , one of the classical model systems for evolutionary developmental biology and regeneration, transcription factor FoxO modulates both stem cell proliferation and innate immunity. This provides strong support for the role of FoxO as a critical rate-of-aging regulator...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29664232/correlation-of-tet2-snp-rs2454206-with-improved-survival-in-children-with-acute-myeloid-leukemia-featuring-intermediate-risk-cytogenetics
#10
Xingjuan Wang, Xi Chen, Zhenzhen Yang, Hu Dou, Ling Lu, Junqin Bi, Lin Zou, Jie Yu, Liming Bao
Single nucleotide polymorphisms (SNPs) may influence the disease course and outcome of hematologic neoplasms. SNP rs2454206 is common in the TET2 gene, which plays a role in epigenetic regulation of myelopoiesis. Few investigations examined the role of TET2 SNP rs2454206 in acute myeloid leukemia (AML) and none of those studies was performed in Chinese populations. Here, we report the prevalence and clinical relevance of TET2 SNP rs2454206 in 254 Chinese patients with childhood AML. Our data demonstrate that TET2 SNP rs2454206AG/GG is associated with improved overall survival and event-free survival in AML patients with intermediate-risk cytogenetics features...
April 17, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29661983/the-evolution-of-cpg-density-and-lifespan-in-conserved-primate-and-mammalian-promoters
#11
Adam T McLain, Christopher Faulk
Gene promoters are evolutionarily conserved across holozoans and enriched in CpG sites, the target for DNA methylation. As animals age, the epigenetic pattern of DNA methylation degrades, with highly methylated CpG sites gradually becoming demethylated while CpG islands increase in methylation. Across vertebrates, aging is a trait that varies among species. We used this variation to determine whether promoter CpG density correlates with species' maximum lifespan. Human promoter sequences were used to identify conserved regions in 131 mammals and a subset of 28 primate genomes...
April 14, 2018: Aging
https://www.readbyqxmd.com/read/29659014/single-cpg-hypermethylation-allele-methylation-errors-and-decreased-expression-of-multiple-tumor-suppressor-genes-in-normal-body-cells-of-mutation-negative-early-onset-and-high-risk-breast-cancer-patients
#12
Julia Böck, Silke Appenzeller, Larissa Haertle, Tamara Schneider, Andrea Gehrig, Jörg Schröder, Simone Rost, Beat Wolf, Claus R Bartram, Christian Sutter, Thomas Haaf
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age-matched controls...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29656664/epigenetic-aging-in-major-depressive-disorder
#13
Laura K M Han, Moji Aghajani, Shaunna L Clark, Robin F Chan, Mohammad W Hattab, Andrey A Shabalin, Min Zhao, Gaurav Kumar, Lin Ying Xie, Rick Jansen, Yuri Milaneschi, Brian Dean, Karolina A Aberg, Edwin J C G van den Oord, Brenda W J H Penninx
OBJECTIVE: Major depressive disorder is associated with an increased risk of mortality and aging-related diseases. The authors examined whether major depression is associated with higher epigenetic aging in blood as measured by DNA methylation (DNAm) patterns, whether clinical characteristics of major depression have a further impact on these patterns, and whether the findings replicate in brain tissue. METHOD: DNAm age was estimated using all methylation sites in blood of 811 depressed patients and 319 control subjects with no lifetime psychiatric disorders and low depressive symptoms from the Netherlands Study of Depression and Anxiety...
April 16, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29643765/mirna-long-term-response-to-early-metabolic-environmental-challenge-in-hypothalamic-arcuate-nucleus
#14
Charlotte Benoit, Soraya Doubi-Kadmiri, Xavier Benigni, Delphine Crepin, Laure Riffault, Ghislaine Poizat, Claire-Marie Vacher, Mohammed Taouis, Anne Baroin-Tourancheau, Laurence Amar
Epidemiological reports and studies using rodent models indicate that early exposure to nutrient and/or hormonal challenges can reprogram metabolism at adulthood. Hypothalamic arcuate nucleus (ARC) integrates peripheral and central signals to adequately regulate energy homeostasis. microRNAs (miRNAs) participate in the control of gene expression of large regulatory networks including many signaling pathways involved in epigenetics regulations. Here, we have characterized and compared the miRNA population of ARC of adult male rats continuously exposed to a balanced metabolic environment to the one of adult male rats exposed to an unbalanced high-fat/high-carbohydrate/moderate-protein metabolic environment during the perinatal period and/or at adulthood that consequently displayed hyperinsulinemia and/or hyperleptinemia...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29643443/dna-methylation-based-biomarkers-and-the-epigenetic-clock-theory-of-ageing
#15
REVIEW
Steve Horvath, Kenneth Raj
Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course...
April 11, 2018: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/29642537/epigenetic-mechanisms-impacting-aging-a-focus-on-histone-levels-and-telomeres
#16
REVIEW
Shufei Song, F Brad Johnson
Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet...
April 9, 2018: Genes
https://www.readbyqxmd.com/read/29627813/pathways-of-association-between-maternal-haemoglobin-and-stillbirth-path-analysis-of-maternity-data-from-two-hospitals-in-england
#17
Manisha Nair, Marian Knight, Susan Robinson, Catherine Nelson-Piercy, Simon J Stanworth, David Churchill
OBJECTIVE: To investigate the mechanisms that link maternal haemoglobin concentration with stillbirth. DESIGN: A retrospective cohort analysis using anonymised maternity data from two hospitals in England. SETTING: The Royal Wolverhampton NHS Trust and Guy's and St Thomas' NHS Foundation Trust. STUDY POPULATION: 12 636 women with singleton pregnancies ≥24 weeks of gestation giving birth in the two hospitals during 2013-2015...
April 7, 2018: BMJ Open
https://www.readbyqxmd.com/read/29626604/transgenerational-effects-of-paternal-dietary-astragalus-polysaccharides-on-spleen-immunity-of-broilers
#18
Yulong Li, Xinyu Lei, Zhenchen Yin, Wei Guo, Shengru Wu, Xiaojun Yang
Our previous study indicated that paternal dietary Astragalus polysaccharides (APS) could induce endotoxin tolerance-like response in jejunum of offspring chickens. There exist positive interaction between intestinal mucosal immunity and systemic immunity. So we studied the transgenerational effect and nutri-epigenetic role of paternal dietary APS on spleen immunity. 64 one-day-old Avein breeder cocks were used in a single-factor design with 0 and 10 g/kg APS, respectively, 4 replicated cages each group, and 8 birds each cage...
April 4, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29626501/birth-weight-predicts-aging-trajectory-a-hypothesis
#19
REVIEW
Alexander M Vaiserman
Increasing evidence suggests that risk for age-related disease and longevity can be programmed early in life. In human populations, convincing evidence has been accumulated indicating that intrauterine growth restriction (IUGR) resulting in low birth weight (<2.5 kg) followed by postnatal catch-up growth is associated with various aspects of metabolic syndrome, type 2 diabetes and cardiovascular disease in adulthood. Fetal macrosomia (birth weight >4.5 kg), by contrast, is associated with high risk of non-diabetic obesity and cancers in later life...
April 4, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29619646/-sarcopenia-and-frailty-in-older-patients-with-rheumatism
#20
U Lange
Sarcopenia is an age-related generalized loss of muscle mass and muscle strength resulting in low physical performance, which can be observed in up to 50% of >80-year-old individuals. The consequences are manifold and sarcopenia is closely linked to frailty. Important risk factors are genetics/epigenetics, immobilization, malnutrition and anorexia, hormone deficiencies, chronic inflammation and raised levels of inhibitory factors of tissue regeneration. Thus, functional assessment of muscle strength and physical performance are central components of diagnosing sarcopenia, beyond the mere quantification of muscle mass...
April 4, 2018: Zeitschrift Für Rheumatologie
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