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Steve Horvath

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https://www.readbyqxmd.com/read/28089957/the-epigenetic-clock-and-physical-development-during-childhood-and-adolescence-longitudinal-analysis-from-a-uk-birth-cohort
#1
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
#2
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/27955697/dna-methylation-signatures-of-chronic-low-grade-inflammation-are-associated-with-complex-diseases
#3
Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M Mendelson, Karen N Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L Waite, Roby Joehanes, Weihua Guan, Jennifer A Brody, Cathy Elks, Riccardo Marioni, Min A Jhun, Golareh Agha, Jan Bressler, Cavin K Ward-Caviness, Brian H Chen, Tianxiao Huan, Kelly Bakulski, Elias L Salfati, Giovanni Fiorito, Simone Wahl, Katharina Schramm, Jin Sha, Dena G Hernandez, Allan C Just, Jennifer A Smith, Nona Sotoodehnia, Luke C Pilling, James S Pankow, Phil S Tsao, Chunyu Liu, Wei Zhao, Simonetta Guarrera, Vasiliki J Michopoulos, Alicia K Smith, Marjolein J Peters, David Melzer, Pantel Vokonas, Myriam Fornage, Holger Prokisch, Joshua C Bis, Audrey Y Chu, Christian Herder, Harald Grallert, Chen Yao, Sonia Shah, Allan F McRae, Honghuang Lin, Steve Horvath, Daniele Fallin, Albert Hofman, Nicholas J Wareham, Kerri L Wiggins, Andrew P Feinberg, John M Starr, Peter M Visscher, Joanne M Murabito, Sharon L R Kardia, Devin M Absher, Elisabeth B Binder, Andrew B Singleton, Stefania Bandinelli, Annette Peters, Melanie Waldenberger, Giuseppe Matullo, Joel D Schwartz, Ellen W Demerath, André G Uitterlinden, Joyce B J van Meurs, Oscar H Franco, Yii-Der Ida Chen, Daniel Levy, Stephen T Turner, Ian J Deary, Kerry J Ressler, Josée Dupuis, Luigi Ferrucci, Ken K Ong, Themistocles L Assimes, Eric Boerwinkle, Wolfgang Koenig, Donna K Arnett, Andrea A Baccarelli, Emelia J Benjamin, Abbas Dehghan
BACKGROUND: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation. RESULTS: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111)...
December 12, 2016: Genome Biology
https://www.readbyqxmd.com/read/27926864/low-cd38-identifies-progenitor-like-inflammation-associated-luminal-cells-that-can-initiate-human-prostate-cancer-and-predict-poor-outcome
#4
Xian Liu, Tristan R Grogan, Haley Hieronymus, Takao Hashimoto, Jack Mottahedeh, Donghui Cheng, Lijun Zhang, Kevin Huang, Tanya Stoyanova, Jung Wook Park, Ruzanna O Shkhyan, Behdokht Nowroozizadeh, Matthew B Rettig, Charles L Sawyers, David Elashoff, Steve Horvath, Jiaoti Huang, Owen N Witte, Andrew S Goldstein
Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38(lo) luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38(lo) luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27919067/genome-wide-changes-in-lncrna-splicing-and-regional-gene-expression-patterns-in-autism
#5
Neelroop N Parikshak, Vivek Swarup, T Grant Belgard, Manuel Irimia, Gokul Ramaswami, Michael J Gandal, Christopher Hartl, Virpi Leppa, Luis de la Torre Ubieta, Jerry Huang, Jennifer K Lowe, Benjamin J Blencowe, Steve Horvath, Daniel H Geschwind
Autism spectrum disorder (ASD) involves substantial genetic contributions. These contributions are profoundly heterogeneous but may converge on common pathways that are not yet well understood. Here, through post-mortem genome-wide transcriptome analysis of the largest cohort of samples analysed so far, to our knowledge, we interrogate the noncoding transcriptome, alternative splicing, and upstream molecular regulators to broaden our understanding of molecular convergence in ASD. Our analysis reveals ASD-associated dysregulation of primate-specific long noncoding RNAs (lncRNAs), downregulation of the alternative splicing of activity-dependent neuron-specific exons, and attenuation of normal differences in gene expression between the frontal and temporal lobes...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27717399/an-epigenetic-clock-for-gestational-age-at-birth-based-on-blood-methylation-data
#6
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
https://www.readbyqxmd.com/read/27702440/epigenetic-aging-and-immune-senescence-in-women-with-insomnia-symptoms-findings-from-the-women-s-health-initiative-study
#7
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...
January 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/27690265/dna-methylation-based-measures-of-biological-age-meta-analysis-predicting-time-to-death
#8
Brian H Chen, Riccardo E Marioni, Elena Colicino, Marjolein J Peters, Cavin K Ward-Caviness, Pei-Chien Tsai, Nicholas S Roetker, Allan C Just, Ellen W Demerath, Weihua Guan, Jan Bressler, Myriam Fornage, Stephanie Studenski, Amy R Vandiver, Ann Zenobia Moore, Toshiko Tanaka, Douglas P Kiel, Liming Liang, Pantel Vokonas, Joel Schwartz, Kathryn L Lunetta, Joanne M Murabito, Stefania Bandinelli, Dena G Hernandez, David Melzer, Michael Nalls, Luke C Pilling, Timothy R Price, Andrew B Singleton, Christian Gieger, Rolf Holle, Anja Kretschmer, Florian Kronenberg, Sonja Kunze, Jakob Linseisen, Christine Meisinger, Wolfgang Rathmann, Melanie Waldenberger, Peter M Visscher, Sonia Shah, Naomi R Wray, Allan F McRae, Oscar H Franco, Albert Hofman, André G Uitterlinden, Devin Absher, Themistocles Assimes, Morgan E Levine, Ake T Lu, Philip S Tsao, Lifang Hou, JoAnn E Manson, Cara L Carty, Andrea Z LaCroix, Alexander P Reiner, Tim D Spector, Andrew P Feinberg, Daniel Levy, Andrea Baccarelli, Joyce van Meurs, Jordana T Bell, Annette Peters, Ian J Deary, James S Pankow, Luigi Ferrucci, Steve Horvath
Estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. We previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, we expanded our original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, we examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality...
September 28, 2016: Aging
https://www.readbyqxmd.com/read/27689435/specific-premature-epigenetic-aging-of-cartilage-in-osteoarthritis
#9
Laura Vidal-Bralo, Yolanda Lopez-Golan, Antonio Mera-Varela, Ignacio Rego-Perez, Steve Horvath, Yuhua Zhang, Álvaro Del Real, Guangju Zhai, Francisco J Blanco, Jose A Riancho, Juan J Gomez-Reino, Antonio Gonzalez
Osteoarthritis (OA) is a disease affecting multiple tissues of the joints in the elderly, but most notably articular cartilage. Premature biological aging has been described in this tissue and in blood cells, suggesting a systemic component of premature aging in the pathogenesis of OA. Here, we have explored epigenetic aging in OA at the local (cartilage and bone) and systemic (blood) levels. Two DNA methylation age-measures (DmAM) were used: the multi-tissue age estimator for cartilage and bone; and a blood-specific biomarker for blood...
September 28, 2016: Aging
https://www.readbyqxmd.com/read/27644593/maintenance-of-age-in-human-neurons-generated-by-microrna-based-neuronal-conversion-of-fibroblasts
#10
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
https://www.readbyqxmd.com/read/27511193/an-epigenetic-clock-analysis-of-race-ethnicity-sex-and-coronary-heart-disease
#11
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...
August 11, 2016: Genome Biology
https://www.readbyqxmd.com/read/27479945/huntington-s-disease-accelerates-epigenetic-aging-of-human-brain-and-disrupts-dna-methylation-levels
#12
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
https://www.readbyqxmd.com/read/27470971/rheology-and-structure-of-surface-crosslinked-surfactant-activated-microgels
#13
Dongcui Li, Raymond Hsu, Brian Figura, Robert Jacobs, Sinan Li, Steve Horvath, Ted Clifford, Krishnan Chari
Nonionic surfactant-activated microgels (SAMs), composed of hydrophobic alkyl acrylates and hydrophilic hydroxyalkyl esters that utilize the effects of surfactant mediated swelling and interaction to provide pH-independent rheological properties, were previously reported as a new pathway to the rheology modification of surfactant solutions. Crosslinking was shown to play an important role in the properties of these soft microgel systems. To understand the impact of crosslinking chemistry on SAM polymers, we have compared two types of SAM polymers: a conventionally crosslinked SAM polymer via allyl pentaerythritol and a novel SAM polymer, where the surface is self-crosslinked via a reactive surfactant...
September 14, 2016: Soft Matter
https://www.readbyqxmd.com/read/27457926/menopause-accelerates-biological-aging
#14
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
https://www.readbyqxmd.com/read/26900923/integrated-genomics-and-proteomics-define-huntingtin-cag-length-dependent-networks-in-mice
#15
Peter Langfelder, Jeffrey P Cantle, Doxa Chatzopoulou, Nan Wang, Fuying Gao, Ismael Al-Ramahi, Xiao-Hong Lu, Eliana Marisa Ramos, Karla El-Zein, Yining Zhao, Sandeep Deverasetty, Andreas Tebbe, Christoph Schaab, Daniel J Lavery, David Howland, Seung Kwak, Juan Botas, Jeffrey S Aaronson, Jim Rosinski, Giovanni Coppola, Steve Horvath, X William Yang
To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients...
April 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/26898779/a-systems-level-analysis-of-the-peripheral-nerve-intrinsic-axonal-growth-program
#16
Vijayendran Chandran, Giovanni Coppola, Homaira Nawabi, Takao Omura, Revital Versano, Eric A Huebner, Alice Zhang, Michael Costigan, Ajay Yekkirala, Lee Barrett, Armin Blesch, Izhak Michaelevski, Jeremy Davis-Turak, Fuying Gao, Peter Langfelder, Steve Horvath, Zhigang He, Larry Benowitz, Mike Fainzilber, Mark Tuszynski, Clifford J Woolf, Daniel H Geschwind
The regenerative capacity of the injured CNS in adult mammals is severely limited, yet axons in the peripheral nervous system (PNS) regrow, albeit to a limited extent, after injury. We reasoned that coordinate regulation of gene expression in injured neurons involving multiple pathways was central to PNS regenerative capacity. To provide a framework for revealing pathways involved in PNS axon regrowth after injury, we applied a comprehensive systems biology approach, starting with gene expression profiling of dorsal root ganglia (DRGs) combined with multi-level bioinformatic analyses and experimental validation of network predictions...
March 2, 2016: Neuron
https://www.readbyqxmd.com/read/26885756/epigenetic-clock-analyses-of-cellular-senescence-and-ageing
#17
Donna Lowe, Steve Horvath, Kenneth Raj
A confounding aspect of biological ageing is the nature and role of senescent cells. It is unclear whether the three major types of cellular senescence, namely replicative senescence, oncogene-induced senescence and DNA damage-induced senescence are descriptions of the same phenomenon instigated by different sources, or if each of these is distinct, and how they are associated with ageing. Recently, we devised an epigenetic clock with unprecedented accuracy and precision based on very specific DNA methylation changes that occur in function of age...
February 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/26876179/mct1-modulates-cancer-cell-pyruvate-export-and-growth-of-tumors-that-co-express-mct1-and-mct4
#18
Candice Sun Hong, Nicholas A Graham, Wen Gu, Carolina Espindola Camacho, Vei Mah, Erin L Maresh, Mohammed Alavi, Lora Bagryanova, Pascal A L Krotee, Brian K Gardner, Iman Saramipoor Behbahan, Steve Horvath, David Chia, Ingo K Mellinghoff, Sara A Hurvitz, Steven M Dubinett, Susan E Critchlow, Siavash K Kurdistani, Lee Goodglick, Daniel Braas, Thomas G Graeber, Heather R Christofk
Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4...
February 23, 2016: Cell Reports
https://www.readbyqxmd.com/read/26830004/genetic-variants-near-mlst8-and-dhx57-affect-the-epigenetic-age-of-the-cerebellum
#19
Ake T Lu, Eilis Hannon, Morgan E Levine, Ke Hao, Eileen M Crimmins, Katie Lunnon, Alexey Kozlenkov, Jonathan Mill, Stella Dracheva, Steve Horvath
DNA methylation (DNAm) levels lend themselves for defining an epigenetic biomarker of aging known as the 'epigenetic clock'. Our genome-wide association study (GWAS) of cerebellar epigenetic age acceleration identifies five significant (P<5.0 × 10(-8)) SNPs in two loci: 2p22.1 (inside gene DHX57) and 16p13.3 near gene MLST8 (a subunit of mTOR complex 1 and 2). We find that the SNP in 16p13.3 has a cis-acting effect on the expression levels of MLST8 (P=6.9 × 10(-18)) in most brain regions. In cerebellar samples, the SNP in 2p22...
2016: Nature Communications
https://www.readbyqxmd.com/read/26689571/accelerated-epigenetic-aging-in-brain-is-associated-with-pre-mortem-hiv-associated-neurocognitive-disorders
#20
Andrew J Levine, Austin Quach, David J Moore, Cristian L Achim, Virawudh Soontornniyomkij, Eliezer Masliah, Elyse J Singer, Benjamin Gelman, Natasha Nemanim, Steve Horvath
HIV infection leads to age-related conditions in relatively young persons. HIV-associated neurocognitive disorders (HAND) are considered among the most prevalent of these conditions. To study the mechanisms underlying this disorder, researchers need an accurate method for measuring biological aging. Here, we apply a recently developed measure of biological aging, based on DNA methylation, to the study of biological aging in HIV+ brains. Retrospective analysis of tissue bank specimens and pre-mortem data was carried out...
June 2016: Journal of Neurovirology
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