Publications by authors named "Horvath S"

In mammals, females generally live longer than males. Nevertheless, the mechanisms underpinning sex-dependent longevity are currently unclear. Epigenetic clocks are powerful biological biomarkers capable of precisely estimating chronological age and identifying novel factors influencing the aging rate using only DNA methylation data.

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Capsular polysaccharides (CPSs) protect bacteria from host and environmental factors. Many bacteria can express different CPSs and these CPSs are phase variable. For example, ) is a prominent member of the human gut microbiome and expresses eight different capsular polysaccharides.

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Background: Knowledge of age-related DNA methylation changes in skeletal muscle is limited, yet this tissue is severely affected by ageing in humans.

Methods: We conducted a large-scale epigenome-wide association study meta-analysis of age in human skeletal muscle from 10 studies (total n = 908 muscle methylomes from men and women aged 18-89 years old). We explored the genomic context of age-related DNA methylation changes in chromatin states, CpG islands, and transcription factor binding sites and performed gene set enrichment analysis.

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Article Synopsis
  • The study investigates genetic and environmental factors influencing biological aging, using DNA methylation data from over 40,000 individuals to identify genetic loci associated with epigenetic aging markers.
  • It identified 137 significant genetic loci, including 113 that were previously unknown, linked to various epigenetic clocks and related biological measurements.
  • The findings suggest a connection between genetic factors, lifestyle choices, and longevity, shedding light on the complex genetics of aging.
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Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies.

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Although the investigation of the epigenome becomes increasingly important, still little is known about the long-term evolution of epigenetic marks and systematic investigation strategies are still lacking. Here, we systematically demonstrate the transfer of classic phylogenetic methods such as maximum likelihood based on substitution models, parsimony, and distance-based to interval-scaled epigenetic data. Using a great apes blood data set, we demonstrate that DNA methylation is evolutionarily conserved at the level of individual CpGs in promotors, enhancers, and genic regions.

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Modern analytical applications of liquid chromatography require more and more efficient columns. In this work, the possibility of utilizing particle size gradient in the chromatographic column was studied by a theoretical approach. In the course of our work three different scenarios of particle size gradients were considered with different shapes (linear, convex and concave).

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Background: DNA methylation-based epigenetic age measures have been used as biological aging markers and are associated with a healthy lifespan. Few population-based studies have examined the relation between diet and epigenetic age acceleration.

Objectives: We aimed to investigate the relation between diet quality and epigenetic age acceleration.

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Age-associated DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elephants. These clocks were developed using novel DNA methylation profiles of 140 elephant blood samples of known age, at loci that are highly conserved between mammalian species, using a custom Infinium array (HorvathMammalMethylChip40).

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Article Synopsis
  • The text is a notice indicating that there is a correction to an article with the DOI reference 10.1016/j.gore.2020.100648.
  • The correction aims to address inaccuracies or errors found in the original publication.
  • Readers are encouraged to refer to the updated information to ensure they have the most accurate understanding of the research.
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Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent hybridization (flow FISH) methods using blood samples from healthy adults.

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Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies.

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Celiac disease (CeD) is a T-cell-dependent enteropathy with autoimmune features where tissue transglutaminase (TG2)-mediated posttranslational modification of gliadin peptides has a decisive role in the pathomechanism. The humoral immune response is reported to target mainly TG2-deamidated γ-gliadin peptides. However, α-gliadin peptides, like p57-68, playing a crucial role in the T-cell response, and p31-43, a major trigger of innate responses, also contain B-cell gliadin epitopes and γ-gliadin like motifs.

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The development of a precise blood or skin tissue DNA Epigenetic Aging Clock for Odontocete (OEAC) would solve current age estimation inaccuracies for wild odontocetes. Therefore, we determined genome-wide DNA methylation profiles using a custom array (HorvathMammalMethyl40) across skin and blood samples (n = 446) from known age animals representing nine odontocete species within 4 phylogenetic families to identify age associated CG dinucleotides (CpGs). The top CpGs were used to create a cross-validated OEAC clock which was highly correlated for individuals (r = 0.

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Background: Mitral valve repair with papillary muscle approximation (MVr-PMA) for severe secondary mitral regurgitation (MR) decreases MR recurrence compared with MVr alone. This study assessed the effects of MVr-PMA on left ventricular (LV) remodeling and shape, systolic function and strain mechanics.

Methods: Forty-eight patients who underwent MVr-PMA for severe secondary MR and had follow-up echocardiograms available for review were identified.

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Objectives: Workplace type 2 diabetes (T2D) prevention programs vary in intervention, delivery and methodologic approaches. Using predetermined criteria, we evaluated the effect and implementation of workplace interventions to prevent T2D.

Methods: We searched Embase, MEDLINE and Cochrane Central Register of Controlled Trials databases from January 2000 to June 2020 to overlap with the launch of the Diabetes Prevention Program (DPP) in 2002.

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Clonal hematopoiesis of indeterminate potential (CHIP) is a common precursor state for blood cancers that most frequently occurs due to mutations in the DNA-methylation modifying enzymes DNMT3A or TET2. We used DNA-methylation array and whole-genome sequencing data from four cohorts together comprising 5522 persons to study the association between CHIP, epigenetic clocks, and health outcomes. CHIP was strongly associated with epigenetic age acceleration, defined as the residual after regressing epigenetic clock age on chronological age, in several clocks, ranging from 1.

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DNA methylation data facilitate the development of accurate molecular estimators of chronological age or "epigenetic clocks." We present a robust epigenetic clock for the beluga whale, , developed for an endangered population in Cook Inlet, Alaska, USA. We used a custom methylation array to measure methylation levels at 37,491 cytosine-guanine sites (CpGs) from skin samples of dead whales ( = 67) whose chronological ages were estimated based on tooth growth layer groups.

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Objectives: There is limited research examining the relationship between alcohol use and eating pathology in men or factors that may moderate this association. The current study investigated the relationship between alcohol use and eating pathology, and examined emotion dysregulation as a moderator of this association, among heavy-drinking college men.

Method: Men mandated to receive an alcohol intervention (N = 88; average age = 19 years) completed questionnaires related to alcohol use, emotion dysregulation, and eating pathology.

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A 67-year-old female with recent hospitalization for pneumonia was transferred to our facility for high fevers and positive blood cultures for staph aureus. During her treatment for pneumonia, central venous catheter was placed. A systolic murmur was found in conjunction with fever and notable premature ventricular contractions on telemetry monitoring.

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Background: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood.

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Sporadic Alzheimer's disease (AD) exclusively affects elderly people. Using direct conversion of AD patient fibroblasts into induced neurons (iNs), we generated an age-equivalent neuronal model. AD patient-derived iNs exhibit strong neuronal transcriptome signatures characterized by downregulation of mature neuronal properties and upregulation of immature and progenitor-like signaling pathways.

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