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Epigenetic clock

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https://www.readbyqxmd.com/read/28303888/dna-methylation-signatures-in-peripheral-blood-strongly-predict-all-cause-mortality
#1
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
#2
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
#3
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...
February 28, 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
#4
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...
February 27, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28198702/epigenetic-clock-analysis-of-diet-exercise-education-and-lifestyle-factors
#5
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
https://www.readbyqxmd.com/read/28098396/effects-of-chronic-cobalt-and-chromium-exposure-after-metal-on-metal-hip-resurfacing-an-epigenome-wide-association-pilot-study
#6
Julia Steinberg, Karan M Shah, Alison Gartland, Eleftheria Zeggini, Jeremy Mark Wilkinson
Metal-on-metal (MOM) hip resurfacing has recently been a popular prosthesis choice for the treatment of symptomatic arthritis, but results in the release of cobalt and chromium ions into the circulation that can be associated with adverse clinical effects. The mechanism underlying these effects remains unclear. While chromosomal aneuploidy and translocations are associated with this exposure, the presence of subtle structural epigenetic modifications in patients with MOM joint replacements remains unexplored...
January 18, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28089957/the-epigenetic-clock-and-physical-development-during-childhood-and-adolescence-longitudinal-analysis-from-a-uk-birth-cohort
#7
Andrew J Simpkin, Laura D Howe, Kate Tilling, Tom R Gaunt, Oliver Lyttleton, Wendy L McArdle, Susan M Ring, Steve Horvath, George Davey Smith, Caroline L Relton
BACKGROUND: Statistical models that use an individual's DNA methylation levels to estimate their age (known as epigenetic clocks) have recently been developed, with 96% correlation found between epigenetic and chronological age. We postulate that differences between estimated and actual age [age acceleration (AA)] can be used as a measure of developmental age in early life. METHODS: We obtained DNA methylation measures at three time points (birth, age 7 years and age 17 years) in 1018 children from the Avon Longitudinal Study of Parents and Children (ALSPAC)...
January 15, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28058013/aging-related-methylation-influences-the-gene-expression-of-key-control-genes-in-colorectal-cancer-and-adenoma
#8
Orsolya Galamb, Alexandra Kalmár, Barbara Kinga Barták, Árpád V Patai, Katalin Leiszter, Bálint Péterfia, Barnabás Wichmann, Gábor Valcz, Gábor Veres, Zsolt Tulassay, Béla Molnár
AIM: To analyze colorectal carcinogenesis and age-related DNA methylation alterations of gene sequences associated with epigenetic clock CpG sites. METHODS: In silico DNA methylation analysis of 353 epigenetic clock CpG sites published by Steve Horvath was performed using methylation array data for a set of 123 colonic tissue samples [64 colorectal cancer (CRC), 42 adenoma, 17 normal; GEO accession number: GSE48684]. Among the differentially methylated age-related genes, secreted frizzled related protein 1 (SFRP1) promoter methylation was further investigated in colonic tissue from 8 healthy adults, 19 normal children, 20 adenoma and 8 CRC patients using bisulfite-specific PCR followed by methylation-specific high resolution melting (MS-HRM) analysis...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28010116/chrono-integrates-behavioral-stress-and-epigenetic-control-of-metabolism
#9
Fumiyuki Hatanaka, Toru Takumi
Circadian rhythms are a critical part of the body's homeostatic mechanisms. These rhythms repeat with a cycle-length of approximately 24 h and are generated by a transcriptional-translational feedback loop. These rhythms are critical for proper behavioral, physiological, and molecular functions. CHRONO, a novel circadian clock gene, forms a complex with other clock proteins and modulates the circadian machinery. CHRONO also interacts with histone deacetylase (HDAC) to modulate the epigenetic status of the transcriptional regulation...
January 19, 2017: Annals of Medicine
https://www.readbyqxmd.com/read/27922611/genetic-and-epigenomic-mechanisms-of-mammalian-circadian-transcription
#10
REVIEW
Romeo Papazyan, Yuxiang Zhang, Mitchell A Lazar
The mammalian molecular clock comprises a complex network of transcriptional programs that integrates environmental signals with physiological pathways in a tissue-specific manner. Emerging technologies are extending knowledge of basic clock features by uncovering their underlying molecular mechanisms, thus setting the stage for a 'systems' view of the molecular clock. Here we discuss how recent data from genome-wide genetic and epigenetic studies have informed the understanding of clock function. In addition to its importance in human physiology and disease, the clock mechanism provides an ideal model to assess general principles of dynamic transcription regulation in vivo...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27889677/blood-dna-methylation-age-is-not-associated-with-cognitive-functioning-in-middle-aged-monozygotic-twins
#11
A Starnawska, Q Tan, A Lenart, M McGue, O Mors, A D Børglum, K Christensen, M Nyegaard, L Christiansen
The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27883893/circadian-alterations-during-early-stages-of-alzheimer-s-disease-are-associated-with-aberrant-cycles-of-dna-methylation-in-bmal1
#12
Peter Cronin, Michael J McCarthy, Andrew S P Lim, David P Salmon, Douglas Galasko, Eliezer Masliah, Philip L De Jager, David A Bennett, Paula Desplats
INTRODUCTION: Circadian alterations are prevalent in Alzheimer's disease (AD) and may contribute to cognitive impairment, behavioral symptoms, and neurodegeneration. Epigenetic mechanisms regulate the circadian clock, and changes in DNA methylation have been reported in AD brains, but the pathways that mediate circadian deregulation in AD are incompletely understood. We hypothesized that aberrant DNA methylation may affect circadian rhythms in AD. METHODS: We investigated DNA methylation, transcription, and expression of BMAL1, a positive regulator of the circadian clock, in cultured fibroblasts and brain samples from two independent cohorts of aging and AD...
November 22, 2016: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/27868040/inhibition-of-mll1-histone-methyltransferase-brings-the-developmental-clock-back-to-na%C3%A3-ve-pluripotency
#13
COMMENT
Stefan Muller, Arnab Nayak
Embryonic stem cells (ESCs) and the post-implantation epiblast stem cells (EpiSCs) portray two different states of pluripotency. They differ with respect to epigenetic signatures, dependency of growth factor signaling circuit and cell morphology. They are interconvertible, however, with poor reconversion efficiency. This is indicative of existence of other unknown regulatory pathways govern developmental stage transition. Zhang and colleagues have recently demonstrated that pharmacological inhibition of MLL1 histone methyltransferase is casually linked to efficient reprogramming of EpiSCs to developmentally competent ESCs...
2016: Stem Cell Investigation
https://www.readbyqxmd.com/read/27859855/dynamic-and-rapid-changes-in-the-transcriptome-and-epigenome-during-germination-and-in-developing-rice-oryza-sativa-coleoptiles-under-anoxia-and-re-oxygenation
#14
Reena Narsai, David Secco, Matthew D Schultz, Joseph R Ecker, Ryan Lister, James Whelan
Detailed molecular profiling of Oryza sativa (rice) was carried out to uncover the features that are essential for germination and early seedling growth under anoxic conditions. Temporal analysis of the transcriptome and methylome from germination to young seedlings under aerobic and anaerobic conditions revealed 82% similarity in the transcriptome and no differences in the epigenome up to 24 h. Following germination, significant changes in the transcriptome and DNA methylation were observed between 4-day aerobically and anaerobically grown coleoptiles...
November 12, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27855491/tick-tock-dna-methylation-the-epigenetic-clock-and-exceptional-longevity
#15
Karen A Mather, Nicola J Armstrong, Anbupalam Thalamuthu, John Bj Kwok
No abstract text is available yet for this article.
December 2016: Epigenomics
https://www.readbyqxmd.com/read/27835646/a-statistical-framework-to-identify-deviation-from-time-linearity-in-epigenetic-aging
#16
Sagi Snir, Bridgett M vonHoldt, Matteo Pellegrini
In multiple studies DNA methylation has proven to be an accurate biomarker of age. To develop these biomarkers, the methylation of multiple CpG sites is typically linearly combined to predict chronological age. By contrast, in this study we apply the Universal PaceMaker (UPM) model to investigate changes in DNA methylation during aging. The UPM was initially developed to study rate acceleration/deceleration in sequence evolution. Rather than identifying which linear combinations of sites predicts age, the UPM models the rates of change of multiple CpG sites, as well as their starting methylation levels, and estimates the age of each individual to optimize the model fit...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27826842/pathways-of-dna-demethylation
#17
Wendy Dean
The regulation of the genome relies on the epigenome to instruct, define and restrict the activities of growth and development. Among the cohort of epigenetic instructions, DNA methylation is perhaps the best understood. In most mammals, cycles of the addition and removal of DNA methylation constitute phases of reprogramming when the developing embryo must negotiate lineage defining and developmental commitment events. In these instances, the DNA methylation instruction is often removed, thereby allowing a change in permission for future development and a return to a more plastic and pluripotent state...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27771773/case-control-study-of-candidate-gene-methylation-and-adenomatous-polyp-formation
#18
M Alexander, J B Burch, S E Steck, C-F Chen, T G Hurley, P Cavicchia, N Shivappa, J Guess, H Zhang, S D Youngstedt, K E Creek, S Lloyd, K Jones, J R Hébert
PURPOSE: Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70-90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation. METHODS: Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors...
February 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/27765932/cisplatin-induced-synthetic-lethality-to-arginine-starvation-therapy-by-transcriptional-suppression-of-ass1-is-regulated-by-dec1-hif-1%C3%AE-and-c-myc-transcription-network-and-is-independent-of-ass1-promoter-dna-methylation
#19
Yan Long, Wen-Bin Tsai, Jeffrey T Chang, Marcos Estecio, Medhi Wangpaichitr, Naramol Savaraj, Lynn G Feun, Helen H W Chen, Macus Tien Kuo
Many human tumors require extracellular arginine (Arg) for growth because the key enzyme for de novo biosynthesis of Arg, argininosuccinate synthetase 1 (ASS1), is silenced. These tumors are sensitive to Arg-starvation therapy using pegylated arginine deiminase (ADI-PEG20) which digests extracellular Arg. Many previous studies reported that ASS1 silencing is due to epigenetic inactivation of ASS1 expression by DNA methylation, and that the demethylation agent 5-aza-deoxycytidine (Aza-dC) can induce ASS1 expression...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27760549/a-new-timepiece-an-epigenetic-mitotic-clock
#20
Brock C Christensen, Karl T Kelsey
A new mitotic clock and mathematical approach that incorporates DNA methylation biology common among human cell types provides a new tool for cancer epigenetics research.
October 19, 2016: Genome Biology
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