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Epigenetic clock

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https://www.readbyqxmd.com/read/28516429/cardinal-epigenetic-role-of-non-coding-regulatory-rnas-in-circadian-rhythm
#1
REVIEW
Utpal Bhadra, Pradipta Patra, Manika Pal-Bhadra
Circadian rhythm which governs basic physiological activities like sleeping, feeding and energy consumption is regulated by light-controlled central clock genes in the pacemaker neuron. The timekeeping machinery with unique transcriptional and post-transcriptional feedback loops is controlled by different small regulatory RNAs in the brain. Roles of the multiple neuronal genes, especially post-transcriptional regulation, splicing, polyadenylation, mature mRNA editing, and stability of translation products, are controlled by epigenetic activities orchestrated via small RNAs...
May 17, 2017: Molecular Neurobiology
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
#2
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/28487473/epigenetic-regulation-of-the-circadian-clock-role-of-5-aza-2-deoxycytidine
#3
Yoshiaki Onishi, Tatsunosuke Tomita, Ryoji Kurita
We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypo-methylated, respectively and that 5-aza-2'-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 hours in RPMI8402 cells...
May 9, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28471941/basic-science-and-pathogenesis-of-ageing-with-hiv-potential-mechanisms-and-biomarkers
#4
Claire Lagathu, Andrea Cossarizza, Véronique Béréziat, Milena Nasi, Jacqueline Capeau, Marcello Pinti
: The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors...
June 1, 2017: AIDS
https://www.readbyqxmd.com/read/28470125/aging-exceptional-longevity-and-comparisons-of-the-hannum-and-horvath-epigenetic-clocks
#5
Nicola J Armstrong, Karen A Mather, Anbupalam Thalamuthu, Margaret J Wright, Julian N Trollor, David Ames, Henry Brodaty, Peter R Schofield, Perminder S Sachdev, John B Kwok
AIM: To examine the relationships between two epigenetic clocks, aging and exceptional longevity. MATERIALS & METHODS: Participants were from three adult cohorts with blood DNA methylation data (Illumina 450 K, n = 275, 34-103 years). Epigenetic age (DNAmage) and age acceleration measures were calculated using the Hannum and Horvath epigenetic clocks. RESULTS: Across all cohorts, DNAmage was correlated with chronological age. In the long-lived cohort (Sydney Centenarian Study; 95+, n = 23), DNAmage was lower than chronological age for both clocks...
May 4, 2017: Epigenomics
https://www.readbyqxmd.com/read/28399939/multi-tissue-dna-methylation-age-predictor-in-mouse
#6
Thomas M Stubbs, Marc Jan Bonder, Anne-Katrien Stark, Felix Krueger, Ferdinand von Meyenn, Oliver Stegle, Wolf Reik
BACKGROUND: DNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. RESULTS: We have generated a comprehensive set of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages...
April 11, 2017: Genome Biology
https://www.readbyqxmd.com/read/28396265/biological-age-predictors
#7
REVIEW
Juulia Jylhävä, Nancy L Pedersen, Sara Hägg
The search for reliable indicators of biological age, rather than chronological age, has been ongoing for over three decades, and until recently, largely without success. Advances in the fields of molecular biology have increased the variety of potential candidate biomarkers that may be considered as biological age predictors. In this review, we summarize current state-of-the-art findings considering six potential types of biological age predictors: epigenetic clocks, telomere length, transcriptomic predictors, proteomic predictors, metabolomics-based predictors, and composite biomarker predictors...
April 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28377537/accelerated-epigenetic-aging-in-werner-syndrome
#8
Anna Maierhofer, Julia Flunkert, Junko Oshima, George M Martin, Thomas Haaf, Steve Horvath
Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0...
April 2017: Aging
https://www.readbyqxmd.com/read/28373722/simulated-microgravity-triggers-epithelial-mesenchymal-transition-in-human-keratinocytes
#9
Danilo Ranieri, Sara Proietti, Simona Dinicola, Maria Grazia Masiello, Benedetta Rosato, Giulia Ricci, Alessandra Cucina, Angela Catizone, Mariano Bizzarri, Maria Rosaria Torrisi
The microgravitational environment is known to affect the cellular behaviour inducing modulation of gene expression and enzymatic activities, epigenetic modifications and alterations of the structural organization. Simulated microgravity, obtained in the laboratory setting through the use of a Random Positioning Machine (RPM), represents a well recognized and useful tool for the experimental studies of the cellular adaptations and molecular changes in response to weightlessness. Short exposure of cultured human keratinocytes to the RPM microgravity influences the cellular circadian clock oscillation...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373601/an-epigenetic-aging-clock-for-dogs-and-wolves
#10
Michael J Thompson, Bridgett vonHoldt, Steve Horvath, Matteo Pellegrini
Several articles describe highly accurate age estimation methods based on human DNA-methylation data. It is not yet known whether similar epigenetic aging clocks can be developed based on blood methylation data from canids. Using Reduced Representation Bisulfite Sequencing, we assessed blood DNA-methylation data from 46 domesticated dogs (Canis familiaris) and 62 wild gray wolves (C. lupus). By regressing chronological dog age on the resulting CpGs, we defined highly accurate multivariate age estimators for dogs (based on 41 CpGs), wolves (67 CpGs), and both combined (115 CpGs)...
March 28, 2017: Aging
https://www.readbyqxmd.com/read/28364215/dna-methylation-age-is-elevated-in-breast-tissue-of-healthy-women
#11
Mary E Sehl, Jill E Henry, Anna Maria Storniolo, Patricia A Ganz, Steve Horvath
BACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference...
March 31, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28361883/migration-phenology-and-breeding-success-are-predicted-by-methylation-of-a-photoperiodic-gene-in-the-barn-swallow
#12
Nicola Saino, Roberto Ambrosini, Benedetta Albetti, Manuela Caprioli, Barbara De Giorgio, Emanuele Gatti, Felix Liechti, Marco Parolini, Andrea Romano, Maria Romano, Chiara Scandolara, Luca Gianfranceschi, Valentina Bollati, Diego Rubolini
Individuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5'-UTR loci of the photoperiodic Clock gene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators...
March 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28352958/the-epigenetic-landscape-of-age-related-diseases-the-geroscience-perspective
#13
Noémie Gensous, Maria Giulia Bacalini, Chiara Pirazzini, Elena Marasco, Cristina Giuliani, Francesco Ravaioli, Giacomo Mengozzi, Claudia Bertarelli, Maria Giustina Palmas, Claudio Franceschi, Paolo Garagnani
In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of "geroscience", which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases...
March 28, 2017: Biogerontology
https://www.readbyqxmd.com/read/28351423/epigenetic-aging-signatures-in-mice-livers-are-slowed-by-dwarfism-calorie-restriction-and-rapamycin-treatment
#14
Tina Wang, Brian Tsui, Jason F Kreisberg, Neil A Robertson, Andrew M Gross, Michael Ku Yu, Hannah Carter, Holly M Brown-Borg, Peter D Adams, Trey Ideker
BACKGROUND: Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. RESULTS: We first examined whether mice and humans experience similar patterns of change in the methylome with age...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28351383/diverse-interventions-that-extend-mouse-lifespan-suppress-shared-age-associated-epigenetic-changes-at-critical-gene-regulatory-regions
#15
John J Cole, Neil A Robertson, Mohammed Iqbal Rather, John P Thomson, Tony McBryan, Duncan Sproul, Tina Wang, Claire Brock, William Clark, Trey Ideker, Richard R Meehan, Richard A Miller, Holly M Brown-Borg, Peter D Adams
BACKGROUND: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging "clock", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 (df/df) mutation, calorie restriction and rapamycin...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28303888/dna-methylation-signatures-in-peripheral-blood-strongly-predict-all-cause-mortality
#16
Yan Zhang, Rory Wilson, Jonathan Heiss, Lutz P Breitling, Kai-Uwe Saum, Ben Schöttker, Bernd Holleczek, Melanie Waldenberger, Annette Peters, Hermann Brenner
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28289477/obesity-accelerates-epigenetic-aging-in-middle-aged-but-not-in-elderly-individuals
#17
Tapio Nevalainen, Laura Kananen, Saara Marttila, Juulia Jylhävä, Nina Mononen, Mika Kähönen, Olli T Raitakari, Antti Hervonen, Marja Jylhä, Terho Lehtimäki, Mikko Hurme
BACKGROUND: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28259012/dna-methylome-analysis-identifies-accelerated-epigenetic-ageing-associated-with-postmenopausal-breast-cancer-susceptibility
#18
Srikant Ambatipudi, Steve Horvath, Flavie Perrier, Cyrille Cuenin, Hector Hernandez-Vargas, Florence Le Calvez-Kelm, Geoffroy Durand, Graham Byrnes, Pietro Ferrari, Liacine Bouaoun, Athena Sklias, Véronique Chajes, Kim Overvad, Gianluca Severi, Laura Baglietto, Françoise Clavel-Chapelon, Rudolf Kaaks, Myrto Barrdahl, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Androniki Naska, Giovanna Masala, Claudia Agnoli, Silvia Polidoro, Rosario Tumino, Salvatore Panico, Martijn Dollé, Petra H M Peeters, N Charlotte Onland-Moret, Torkjel M Sandanger, Therese H Nøst, Elisabete Weiderpass, J Ramón Quirós, Antonio Agudo, Miguel Rodriguez-Barranco, José María Huerta Castaño, Aurelio Barricarte, Ander Matheu Fernández, Ruth C Travis, Paolo Vineis, David C Muller, Elio Riboli, Marc Gunter, Isabelle Romieu, Zdenko Herceg
AIM OF THE STUDY: A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. METHODS: Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples...
April 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28249716/conserved-effect-of-aging-on-dna-methylation-and-association-with-ezh2-polycomb-protein-in-mice-and-humans
#19
Khyobeni Mozhui, Ashutosh K Pandey
In humans, DNA methylation at specific CpG sites can be used to estimate the 'epigenetic clock', a biomarker of aging and health. The mechanisms that regulate the aging epigenome and level of conservation are not entirely clear. We performed affinity-based enrichment with methyl-CpG binding domain protein followed by high-throughput sequencing (MBD-seq) to assay DNA methylation in mouse samples. Consistent with previous reports, aging is associated with increase in methylation at CpG islands that likely overlap regulatory regions of genes that have been implicated in cancers (e...
March 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28198702/epigenetic-clock-analysis-of-diet-exercise-education-and-lifestyle-factors
#20
Austin Quach, Morgan E Levine, Toshiko Tanaka, Ake T Lu, Brian H Chen, Luigi Ferrucci, Beate Ritz, Stefania Bandinelli, Marian L Neuhouser, Jeannette M Beasley, Linda Snetselaar, Robert B Wallace, Philip S Tsao, Devin Absher, Themistocles L Assimes, James D Stewart, Yun Li, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Steve Horvath
Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions, and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti...
February 14, 2017: Aging
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