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Epigenetic clock

Susanne A Bengesser, Eva Z Reininghaus, Nina Lackner, Armin Birner, Frederike T Fellendorf, Martina Platzer, Nora Kainzbauer, Bernhard Tropper, Christa Hörmanseder, Robert Queissner, Hans-Peter Kapfhammer, Sandra J Wallner-Liebmann, Robert Fuchs, Erwin Petek, Christian Windpassinger, Mario Schnalzenberger, Bernd Reininghaus, Bernd Evert, Andreas Waha
OBJECTIVES: The clock gene ARNTL is associated with the transcription activation of monoamine oxidase A according to previous literature. Thus, we hypothesised that methylation of ARNTL may differ between bipolar disorder (BD) and controls. METHODS: The methylation status of one CpG island covering the first exon of ARNTL (PS2) and one site in the 5' region of ARNTL (cg05733463) were analysed in patients with BD (n = 151) versus controls (n = 66). Methylation analysis was performed by bisulphite-conversion of DNA from fasting blood with the EpiTect Bisulfite Kit, PCR and pyrosequencing...
October 14, 2016: World Journal of Biological Psychiatry
Anna K Knight, Jeffrey M Craig, Christiane Theda, Marie Bækvad-Hansen, Jonas Bybjerg-Grauholm, Christine S Hansen, Mads V Hollegaard, David M Hougaard, Preben B Mortensen, Shantel M Weinsheimer, Thomas M Werge, Patricia A Brennan, Joseph F Cubells, D Jeffrey Newport, Zachary N Stowe, Jeanie L Y Cheong, Philippa Dalach, Lex W Doyle, Yuk J Loke, Andrea A Baccarelli, Allan C Just, Robert O Wright, Mara M Téllez-Rojo, Katherine Svensson, Letizia Trevisi, Elizabeth M Kennedy, Elisabeth B Binder, Stella Iurato, Darina Czamara, Katri Räikkönen, Jari M T Lahti, Anu-Katriina Pesonen, Eero Kajantie, Pia M Villa, Hannele Laivuori, Esa Hämäläinen, Hea Jin Park, Lynn B Bailey, Sasha E Parets, Varun Kilaru, Ramkumar Menon, Steve Horvath, Nicole R Bush, Kaja Z LeWinn, Frances A Tylavsky, Karen N Conneely, Alicia K Smith
BACKGROUND: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. RESULTS: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples...
October 7, 2016: Genome Biology
Zhen Yang, Andrew Wong, Diana Kuh, Dirk S Paul, Vardhman K Rakyan, R David Leslie, Shijie C Zheng, Martin Widschwendter, Stephan Beck, Andrew E Teschendorff
BACKGROUND: Variation in cancer risk among somatic tissues has been attributed to variations in the underlying rate of stem cell division. For a given tissue type, variable cancer risk between individuals is thought to be influenced by extrinsic factors which modulate this rate of stem cell division. To date, no molecular mitotic clock has been developed to approximate the number of stem cell divisions in a tissue of an individual and which is correlated with cancer risk. RESULTS: Here, we integrate mathematical modeling with prior biological knowledge to construct a DNA methylation-based age-correlative model which approximates a mitotic clock in both normal and cancer tissue...
October 3, 2016: Genome Biology
Andrea Romano, Barbara De Giorgio, Marco Parolini, Chiara Favero, Cristina Daniela Possenti, Simona Iodice, Manuela Caprioli, Diego Rubolini, Roberto Ambrosini, Luca Gianfranceschi, Nicola Saino, Valentina Bollati
The consequences of exposure to particulate matter (PM) have been thoroughly investigated in humans and other model species, but there is a dearth of studies of the effects of PM on physiology and life-history traits of non-human organisms living in natural or semi-natural environments. Besides toxicological relevance, PM has been recently suggested to exert epigenetic effects by altering DNA methylation patterns. Here, we investigated for the first time the association between the exposure to free-air PM10 and DNA methylation at two loci ('poly-Q exon' and '5'-UTR') of the Clock gene in blood cells of the nestlings of a synanthropic passerine bird, the barn swallow (Hirundo rustica)...
October 3, 2016: Environmental Pollution
Judith E Carroll, Michael R Irwin, Morgan Levine, Teresa E Seeman, Devin Absher, Themistocles Assimes, Steve Horvath
BACKGROUND: Insomnia symptoms are associated with vulnerability to age-related morbidity and mortality. Cross-sectional data suggest that accelerated biological aging may be a mechanism through which sleep influences risk. A novel method for determining age acceleration using epigenetic methylation to DNA has demonstrated predictive utility as an epigenetic clock and prognostic of age-related morbidity and mortality. METHODS: We examined the association of epigenetic age and immune cell aging with sleep in the Women's Health Initiative study (N = 2078; mean 64...
July 26, 2016: Biological Psychiatry
Christine J Huh, Bo Zhang, Matheus B Victor, Sonika Dahiya, Luis Fz Batista, Steve Horvath, Andrew S Yoo
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures...
September 20, 2016: ELife
Michael Verwey, Sabine Dhir, Shimon Amir
Circadian clock proteins form an autoregulatory feedback loop that is central to the endogenous generation and transmission of daily rhythms in behavior and physiology. Increasingly, circadian rhythms in clock gene expression are being reported in diverse tissues and brain regions that lie outside of the suprachiasmatic nucleus (SCN), the master circadian clock in mammals. For many of these extra-SCN rhythms, however, the region-specific implications are still emerging. In order to gain important insights into the potential behavioral, physiological, and psychological relevance of these daily oscillations, researchers have begun to focus on describing the neurochemical, hormonal, metabolic, and epigenetic contributions to the regulation of these rhythms...
2016: F1000Research
Adonis Sfera, Carolina Osorio, Luzmin Inderias, Michael Cummings
BACKGROUND: Exposed to antipsychotic drugs (APDs), older individuals with dementing illness are at risk of cerebrovascular adverse effects (CVAE), including sudden death. Transient microvascular dysfunctions are known to occur in younger persons exposed to APDs; however, they seldom progress to CVAE, suggesting that APDs alone are insufficient for engendering this untoward effect. It is, therefore, believed that a preexistent microvascular damage is necessary for CVAE to take place, but the exact nature of this lesion remains unclear...
2016: Frontiers in Endocrinology
Steve Horvath, Michael Gurven, Morgan E Levine, Benjamin C Trumble, Hillard Kaplan, Hooman Allayee, Beate R Ritz, Brian Chen, Ake T Lu, Tammy M Rickabaugh, Beth D Jamieson, Dianjianyi Sun, Shengxu Li, Wei Chen, Lluis Quintana-Murci, Maud Fagny, Michael S Kobor, Philip S Tsao, Alexander P Reiner, Kerstin L Edlefsen, Devin Absher, Themistocles L Assimes
BACKGROUND: Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors...
2016: Genome Biology
Qihua Tan, Bastiaan T Heijmans, Jacob V B Hjelmborg, Mette Soerensen, Kaare Christensen, Lene Christiansen
BACKGROUND: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process. METHODS: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years)...
August 6, 2016: International Journal of Epidemiology
Niels H H Heegaard, Anting Liu Carlsen, Berit Lilje, Kim Lee Ng, Mette E Rønne, Henrik L Jørgensen, Henriette Sennels, Jan Fahrenkrug
A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks). The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples...
2016: PloS One
Steve Horvath, Peter Langfelder, Seung Kwak, Jeff Aaronson, Jim Rosinski, Thomas F Vogt, Marika Eszes, Richard L M Faull, Maurice A Curtis, Henry J Waldvogel, Oi-Wa Choi, Spencer Tung, Harry V Vinters, Giovanni Coppola, X William Yang
Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls...
July 2016: Aging
Morgan E Levine, Ake T Lu, Brian H Chen, Dena G Hernandez, Andrew B Singleton, Luigi Ferrucci, Stefania Bandinelli, Elias Salfati, JoAnn E Manson, Austin Quach, Cynthia D J Kusters, Diana Kuh, Andrew Wong, Andrew E Teschendorff, Martin Widschwendter, Beate R Ritz, Devin Absher, Themistocles L Assimes, Steve Horvath
Although epigenetic processes have been linked to aging and disease in other systems, it is not yet known whether they relate to reproductive aging. Recently, we developed a highly accurate epigenetic biomarker of age (known as the "epigenetic clock"), which is based on DNA methylation levels. Here we carry out an epigenetic clock analysis of blood, saliva, and buccal epithelium using data from four large studies: the Women's Health Initiative (n = 1,864); Invecchiare nel Chianti (n = 200); Parkinson's disease, Environment, and Genes (n = 256); and the United Kingdom Medical Research Council National Survey of Health and Development (n = 790)...
August 16, 2016: Proceedings of the National Academy of Sciences of the United States of America
Jianshi Jin, Tengfei Lian, Chan Gu, Kai Yu, Yi Qin Gao, Xiao-Dong Su
DNA methylation on CpG sites is the most common epigenetic modification. Recently, methylation in a non-CpG context was found to occur widely on genomic DNA. Moreover, methylation of non-CpG sites is a highly controlled process, and its level may vary during cellular development. To study non-CpG methylation effects on DNA/protein interactions, we have chosen three human transcription factors (TFs): glucocorticoid receptor (GR), brain and muscle ARNT-like 1 (BMAL1) - circadian locomotor output cycles kaput (CLOCK) and estrogen receptor (ER) with methylated or unmethylated DNA binding sequences, using single-molecule and isothermal titration calorimetry assays...
2016: Scientific Reports
E Reszka, M Przybek
Exploring the putative impact of circadian rhythms is a relatively novel approach to illuminating hormone-related female breast cancer etiology and prognosis. One of several proposed mechanisms underlying breast cancer risk among individuals exposed to light at night involves circadian gene alterations. Although in vitro and animal studies indicate a key role of circadian genes in breast tumor suppression, there is a paucity of data on the role of circadian genes in human breast cancer. This review summarizes recent findings of circadian gene expression and DNA methylation profile from human breast cancer studies in relation to hormonal status, clinicopathological features of tumors, and exposure to night shift work...
2016: Advances in Clinical Chemistry
J Lopez-Minguez, P Gómez-Abellán, M Garaulet
It is known that our physiology changes throughout the day and that several physiological hormones display circadian rhythmicity. The alteration of this normal pattern is called chronodisruption (CD). In recent years, it has been demonstrated that CD is related to obesity. Although several factors may be causing CD, one important aspect to consider is the failure in our internal clock. Indeed, studies performed in mutant animals have demonstrated that mutations in clock genes are related to obesity. In human subjects, mutations are rare (<1 % of the population)...
June 24, 2016: Proceedings of the Nutrition Society
Kelly A Jones, Ji Eun Han, Jason P DeBruyne, Benjamin D Philpot
Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. The paternal UBE3A/Ube3a allele becomes epigenetically silenced in most neurons during postnatal development in humans and mice; hence, loss of the maternal allele largely eliminates neuronal expression of UBE3A protein. However, recent studies suggest that paternal Ube3a may escape silencing in certain neuron populations, allowing for persistent expression of paternal UBE3A protein...
2016: Scientific Reports
L Kananen, S Marttila, T Nevalainen, L Kummola, I Junttila, N Mononen, M Kähönen, O T Raitakari, A Hervonen, M Jylhä, T Lehtimäki, M Hurme, J Jylhävä
The epigenetic clock, defined as the DNA methylome age (DNAmAge), is a candidate biomarker of ageing. In this study, we aimed to characterize the behaviour of this marker during the human lifespan in more detail using two follow-up cohorts (the Young Finns study, calendar age i.e. cAge range at baseline 15-24 years, 25-year-follow-up, N = 183; The Vitality 90+ study, cAge range at baseline 19-90 years, 4-year-follow-up, N = 48). We also aimed to assess the relationship between DNAmAge estimate and the blood cell distributions, as both of these measures are known to change as a function of age...
June 2016: Age (2005-)
Laura Perna, Yan Zhang, Ute Mons, Bernd Holleczek, Kai-Uwe Saum, Hermann Brenner
BACKGROUND: Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality. RESULTS: DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated...
2016: Clinical Epigenetics
Marcel Quint, Carolin Delker, Keara A Franklin, Philip A Wigge, Karen J Halliday, Martijn van Zanten
Temperature is a major factor governing the distribution and seasonal behaviour of plants. Being sessile, plants are highly responsive to small differences in temperature and adjust their growth and development accordingly. The suite of morphological and architectural changes induced by high ambient temperatures, below the heat-stress range, is collectively called thermomorphogenesis. Understanding the molecular genetic circuitries underlying thermomorphogenesis is particularly relevant in the context of climate change, as this knowledge will be key to rational breeding for thermo-tolerant crop varieties...
2016: Nature Plants
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