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Epigenetic clock

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https://www.readbyqxmd.com/read/29643443/dna-methylation-based-biomarkers-and-the-epigenetic-clock-theory-of-ageing
#1
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/29614968/biological-clocks-and-physical-functioning-in-monozygotic-female-twins
#2
Elina Sillanpää, Eija K Laakkonen, Elina Vaara, Taina Rantanen, Vuokko Kovanen, Sarianna Sipilä, Jaakko Kaprio, Miina Ollikainen
BACKGROUND: Biomarkers of biological aging - DNA methylation age (DNAm age) and leukocyte telomere length (LTL)- correlate strongly with chronological age across the life course. It is, however, unclear how these measures of cellular wear and tear are associated with muscle strength and functional capacity, which are known to decline with older age and are associated with mortality. We investigated if DNAm age and LTL were associated with body composition and physical functioning by examining 48 monozygotic twin sisters...
April 4, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/29593783/perinatal-programming-of-circadian-clock-stress-crosstalk
#3
REVIEW
Mariana Astiz, Henrik Oster
An intact communication between circadian clocks and the stress system is important for maintaining physiological homeostasis under resting conditions and in response to external stimuli. There is accumulating evidence for a reciprocal interaction between both-from the systemic to the molecular level. Disruption of this interaction by external factors such as shiftwork, jetlag, or chronic stress increases the risk of developing metabolic, immune, or mood disorders. From experiments in rodents, we know that both systems maturate during the perinatal period...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29567492/paternal-cocaine-disrupts-offspring-circadian-clock-function-in-a-sex-dependent-manner-in-mice
#4
Alexandra M Yaw, Robert W Woodruff, Rebecca A Prosser, J David Glass
The present study is the first to explore the multigenerational effects of mammalian paternal cocaine intake on offspring (F1) circadian clock regulation. Parental cocaine use poses significant health risks to the offspring, through both maternal and paternal drug influences. With respect to the latter, recent evidence suggests that a paternal mode of cocaine inheritance involves epigenetic germ line actions that can ultimately disrupt offspring behavior. Based on our previous report in mice that free-running circadian period (tau) is chronically lengthened following withdrawal from long term cocaine treatment, the present study was undertaken to explore potential epigenetic effects of paternal exposure to cocaine over the ∼40 day murine spermatogenic cycle on F1 circadian regulatory functions...
March 19, 2018: Neuroscience
https://www.readbyqxmd.com/read/29555673/epigenetic-age-acceleration-a-biological-doomsday-clock-for-cardiovascular-disease
#5
EDITORIAL
Michael M Mendelson
No abstract text is available yet for this article.
March 2018: Circulation. Genomic and precision medicine
https://www.readbyqxmd.com/read/29554203/molecular-aging-of-human-liver-an-epigenetic-transcriptomic-signature
#6
Maria Giulia Bacalini, Claudio Franceschi, Davide Gentilini, Francesco Ravaioli, Xiaoyuan Zhou, Daniel Remondini, Chiara Pirazzini, Cristina Giuliani, Elena Marasco, Noémie Gensous, Anna Maria Di Blasio, Ewa Ellis, Roberto Gramignoli, Gastone Castellani, Miriam Capri, Stephen Strom, Christine Nardini, Matteo Cescon, Gian Luca Grazi, Paolo Garagnani
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes...
March 15, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29529061/profiling-dna-methylation-differences-between-inbred-mouse-strains-on-the-illumina-human-infinium-methylationepic-microarray
#7
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
https://www.readbyqxmd.com/read/29524919/placental-circadian-pathway-methylation-and-in-utero-exposure-to-fine-particle-air-pollution
#8
Tim S Nawrot, Nelly D Saenen, Julie Schenk, Bram G Janssen, Valeria Motta, Letizia Tarantini, Bianca Cox, Wouter Lefebvre, Charlotte Vanpoucke, Cristina Maggioni, Valentina Bollati
In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5 ) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing...
March 7, 2018: Environment International
https://www.readbyqxmd.com/read/29514134/methylomic-survival-predictors-frailty-and-mortality
#9
Yan Zhang, Kai-Uwe Saum, Ben Schöttker, Bernd Holleczek, Hermann Brenner
Survival predictors are of potential use for informing on biological age and targeting prevention of aging-related morbidity. We assessed associations of 2 novel methylomic survival indicators, a methylation-based mortality risk score (MRscore) and the epigenetic clock-derived age acceleration (AA), with a well-known survival predictor, frailty index (FI), and compared the 3 indicators in mortality prediction. In a large population-based cohort with 14-year follow-up, we found both MRscore and AA to be independently associated with FI, but the association was much stronger for MRscore than for AA...
March 6, 2018: Aging
https://www.readbyqxmd.com/read/29492790/gene-expression-hallmarks-of-cellular-ageing
#10
Stephen Frenk, Jonathan Houseley
Ageing leads to dramatic changes in the physiology of many different tissues resulting in a spectrum of pathology. Nonetheless, many lines of evidence suggest that ageing is driven by highly conserved cell intrinsic processes, and a set of unifying hallmarks of ageing has been defined. Here, we survey reports of age-linked changes in basal gene expression across eukaryotes from yeast to human and identify six gene expression hallmarks of cellular ageing: downregulation of genes encoding mitochondrial proteins; downregulation of the protein synthesis machinery; dysregulation of immune system genes; reduced growth factor signalling; constitutive responses to stress and DNA damage; dysregulation of gene expression and mRNA processing...
February 28, 2018: Biogerontology
https://www.readbyqxmd.com/read/29432558/models-of-epigenetic-age-capture-patterns-of-dna-methylation-in-glioma-associated-with-molecular-subtype-survival-and-recurrence
#11
Peter Liao, Quinn T Ostrom, Lindsay Stetson, Jill S Barnholtz-Sloan
Background: Models of epigenetic aging (epigenetic clocks) have been implicated as potentially useful markers for cancer risk and prognosis. Using two previously published methods for modeling epigenetic age, Horvath's clock and epiTOC, we investigated epigenetic aging patterns related to WHO grade and molecular subtype as well as associations of epigenetic aging with glioma survival and recurrence. Methods: Epigenetic ages were calculated using Horvath's clock and epiTOC on 516 lower grade glioma and 141 glioblastoma cases along with 136 non-tumor (normal) brain samples...
February 8, 2018: Neuro-oncology
https://www.readbyqxmd.com/read/29374233/gwas-of-epigenetic-aging-rates-in-blood-reveals-a-critical-role-for-tert
#12
Ake T Lu, Luting Xue, Elias L Salfati, Brian H Chen, Luigi Ferrucci, Daniel Levy, Roby Joehanes, Joanne M Murabito, Douglas P Kiel, Pei-Chien Tsai, Idil Yet, Jordana T Bell, Massimo Mangino, Toshiko Tanaka, Allan F McRae, Riccardo E Marioni, Peter M Visscher, Naomi R Wray, Ian J Deary, Morgan E Levine, Austin Quach, Themistocles Assimes, Philip S Tsao, Devin Absher, James D Stewart, Yun Li, Alex P Reiner, Lifang Hou, Andrea A Baccarelli, Eric A Whitsel, Abraham Aviv, Alexia Cardona, Felix R Day, Nicholas J Wareham, John R B Perry, Ken K Ong, Kenneth Raj, Kathryn L Lunetta, Steve Horvath
DNA methylation age is an accurate biomarker of chronological age and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study of 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic age acceleration (IEAA) and gene variants in three loci associated with extrinsic epigenetic age acceleration (EEAA). Mendelian randomization analysis suggests causal influences of menarche and menopause on IEAA and lipoproteins on IEAA and EEAA...
January 26, 2018: Nature Communications
https://www.readbyqxmd.com/read/29367468/dna-methylation-signatures-reflect-aging-in-patients-with-nonalcoholic-steatohepatitis
#13
Rohit Loomba, Yevgeniy Gindin, Zhaoshi Jiang, Eric Lawitz, Stephen Caldwell, C Stephen Djedjos, Ren Xu, Chuhan Chung, Robert P Myers, G Mani Subramanian, Zachary Goodman, Michael Charlton, Nezam H Afdhal, Anna Mae Diehl
A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a measure of human chronological and biological age. We determined peripheral blood DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether accelerated aging occurs in these patients. DNAm signatures were obtained in patients with biopsy-proven NASH and stage 2-3 fibrosis. The DNAm profile from one test and two validation cohorts served as controls. Age acceleration was calculated as the difference between DNAm age and the predicted age based on the linear model derived from controls...
January 25, 2018: JCI Insight
https://www.readbyqxmd.com/read/29337038/back-to-the-future-epigenetic-clock-plasticity-towards-healthy-aging
#14
REVIEW
Ken Declerck, Wim Vanden Berghe
Aging is the most important risk factor for major human lifestyle diseases, including cancer, neurological and cardiometabolic disorders. Due to the complex interplay between genetics, lifestyle and environmental factors, some individuals seem to age faster than others, whereas centenarians seem to have a slower aging process. Therefore, a biochemical biomarker reflecting the relative biological age would be helpful to predict an individual's health status and aging disease risk. Although it is already known for years that cumulative epigenetic changes occur upon aging, DNA methylation patterns were only recently used to construct an epigenetic clock predictor for biological age, which is a measure of how well your body functions compared to your chronological age...
January 11, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29321814/the-epigenetic-clock-and-objectively-measured-sedentary-and-walking-behavior-in-older-adults-the-lothian-birth-cohort-1936
#15
Catharine R Gale, Riccardo E Marioni, Iva Čukić, Sebastien F Chastin, Philippa M Dall, Manon L Dontje, Dawn A Skelton, Ian J Deary
Background: Estimates of biological age derived from DNA-methylation patterns-known as the epigenetic clock-are associated with mortality, physical and cognitive function, and frailty, but little is known about their relationship with sedentary behavior or physical activity. We investigated the cross-sectional relationship between two such estimates of biological age and objectively measured sedentary and walking behavior in older people. Methods: Participants were 248 members of the Lothian Birth Cohort 1936...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29258983/genetic-and-epigeneticregulations-of-mammalian-circadian-rhythms
#16
REVIEW
Min Yue, Yu Yang, Gai Li Guo, Xi Ming Qin
The circadian clocks are vital to many organisms for their survival and adaption to the surrounding environment. More and more people are interested in the circadian clock and related researches. One of the key characteristics of this endogenous clock is its periodicity. Mechanisms underlying the mammalian circadian rhythms with ~24 h periodicity involve interlocked transcriptional and translational feedback loops. The circadian clock system in mammals consists of hierarchical structures, with the suprachiasmatic nucleus (SCN) as the central pacemaker and peripheral oscillators in other organs...
December 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29235933/faster-ticking-rate-of-the-epigenetic-clock-is-associated-with-faster-pubertal-development-in-girls
#17
Alexandra M Binder, Camila Corvalan, Verónica Mericq, Ana Pereira, José Luis Santos, Steve Horvath, John Shepherd, Karin B Michels
Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4)...
2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29225347/accelerated-epigenetic-aging-and-mitochondrial-dna-copy-number-in-bipolar-disorder
#18
Gabriel R Fries, Isabelle E Bauer, Giselli Scaini, Mon-Ju Wu, Iram F Kazimi, Samira S Valvassori, Giovana Zunta-Soares, Consuelo Walss-Bass, Jair C Soares, Joao Quevedo
Bipolar disorder (BD) has been previously associated with accelerated aging; yet, the mechanisms underlying this association are largely unknown. The epigenetic clock has been increasingly recognized as a valuable aging marker, although its association with other biological clocks in BD patients and high-risk subjects, such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been investigated. We included 22 patients with BD I, 16 siblings of BD patients, and 20 healthy controls in this analysis...
December 11, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29221677/epigenetic-regulation-of-biological-rhythms-an-evolutionary-ancient-molecular-timer
#19
REVIEW
Tyler J Stevenson
Biological rhythms are pervasive in nature, yet our understanding of the molecular mechanisms that govern timing is far from complete. The rapidly emerging research focus on epigenetic plasticity has revealed a system that is highly dynamic and reversible. In this Opinion, I propose an epigenetic clock model that outlines how molecular modifications, such as DNA methylation, are integral components for timing endogenous biological rhythms. The hypothesis proposed is that an epigenetic clock serves to maintain the period of molecular rhythms via control over the phase of gene transcription and this timing mechanism resides in all cells, from unicellular to complex organisms...
December 5, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/29190382/the-epigenetic-clock-and-telomere-length-are-independently-associated-with-chronological-age-and-mortality
#20
Riccardo E Marioni, Sarah E Harris, Sonia Shah, Allan F McRae, Thomas von Zglinicki, Carmen Martin-Ruiz, Naomi R Wray, Peter M Visscher, Ian J Deary
No abstract text is available yet for this article.
February 1, 2018: International Journal of Epidemiology
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