A5083296939- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Dementia and Cognitive Impairment Research
- Genetics and Neurodevelopmental Disorders
- Health, Environment, Cognitive Aging
- Genetic Syndromes and Imprinting
- Tryptophan and brain disorders
- Birth, Development, and Health
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- Circadian rhythm and melatonin
- Dietary Effects on Health
- Functional Brain Connectivity Studies
- Alzheimer's disease research and treatments
- Intergenerational Family Dynamics and Caregiving
- RNA modifications and cancer
- Molecular Biology Techniques and Applications
- ATP Synthase and ATPases Research
- Frailty in Older Adults
- Schizophrenia research and treatment
- GDF15 and Related Biomarkers
- Diet and metabolism studies
- Bioinformatics and Genomic Networks
- Immune responses and vaccinations
- Mitochondrial Function and Pathology
Yale University
2019-2025
VA Connecticut Healthcare System
2021-2023
Clinical Trial Investigators
2023
RELX Group (Netherlands)
2023
Yale New Haven Hospital
2018
Abstract Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present fatigue and multi-system disorders, are often lean, die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients diseases ( n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism . We examine phenomenon longitudinally in patient-derived fibroblasts multiple donors....
ABSTRACT Epigenetic clocks have come to be regarded as powerful tools for estimating aging. However, a major drawback in their application is our lack of mechanistic understanding. We hypothesize that uncovering the underlying biology difficult due fact epigenetic are multifactorial composites: They comprised disparate parts, each with own causal mechanism and functional consequences. Thus, only by deconstructing clock signals will it possible glean biological insight. Here we clustered...
Stress triggers anticipatory physiological responses that promote survival, a phenomenon termed allostasis. However, the chronic activation of energy-dependent allostatic results in load, dysregulated state predicts functional decline, accelerates aging, and increases mortality humans. The energetic cost cellular basis for damaging effects load have not been defined. Here, by longitudinally profiling three unrelated primary human fibroblast lines across their lifespan, we find glucocorticoid...
Individuals, organs, tissues, and cells age in diverse ways throughout the lifespan. Epigenetic clocks attempt to quantify differential aging between individuals, but they typically summarize as a single measure, ignoring within-person heterogeneity. Our aim was develop novel systems-based methylation that, when assessed blood, capture distinct physiological systems. We combined supervised unsupervised machine learning methods link DNA methylation, system-specific clinical chemistry...
The host epigenetic landscape rapidly changes during SARS-CoV-2 infection, and evidence suggest that severe COVID-19 is associated with durable scars to the epigenome. Specifically, aberrant DNA methylation in immune cells alterations clocks blood relate COVID-19. However, a longitudinal assessment of states from healthy individuals prior following test-confirmed non-hospitalized has not been performed. Moreover, impact mRNA vaccines upon epigenome remains understudied. Here, we first...
Aging is associated with dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are unknown. Our ability experimentally uncover mechanisms epigenetic aging will be greatly enhanced by our study manipulate these using in vitro models. However, it remains unclear whether elicited cells culture can serve as a model what observed tissues vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) assessed DNAm at each time point via...
Aging is a leading risk factor for cancer. While it proposed that age-related accumulation of somatic mutations drives this relationship, likely not the full story. We show aging and cancer share common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro tested on clinical tissues. This termed CellDRIFT, increased with age across multiple tissues, distinguished tumor normal tissue, was escalated breast tissue...
Alzheimer's disease (AD) risk increases exponentially with age and is associated multiple molecular hallmarks of aging, one which epigenetic alterations. Epigenetic predictors based on 5' cytosine methylation (DNAm), or clocks, have previously suggested that acceleration may occur in AD brain tissue. clocks are promising tools for the quantification biological yet we hypothesize investigation aging will be assisted by development brain-specific clocks. Therefore, generated a novel predictor...
Abstract DNA methylation is a critical epigenetic modification that regulates gene expression and plays significant role in development disease processes. Here, we present the Cytosine-phosphate-Guanine Pretrained Transformer (CpGPT), novel foundation model pretrained on over 1,500 datasets encompassing 100,000 samples from diverse tissues conditions. CpGPT leverages an improved transformer architecture to learn comprehensive representations of patterns, allowing it impute reconstruct...
Abstract Background Epigenetic clocks are promising tools for the study of aging in humans. The quantify biological above and beyond chronological age, demonstrate systematic associations with risk factors that accelerate aging, predict age-related morbidity mortality. There is interest using them as surrogate endpoints intervention studies. However, large number clocks, decentralized publication explosive popularity last decade has made poor accessibility standardization. This hampered...
Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes—those remain unchanged throughout process? These also have a practical application: they serve as reference in expression studies. Reference mostly been identified and validated young organisms, no systematic investigation has done across lifespan. Here, build upon common pipeline for identifying RNA-seq datasets to identify seventeen C57BL/6 mouse tissues (brain, lung, bone...
Abstract Background Measures of epigenetic age have been linked to life circumstances and health outcomes in older populations. The similarity these relationships across multiple populations well-harmonized data has not addressed. We examine links between age, based on currently widely used indicators key the Republic Ireland, United States, Northern Ireland with harmonized, nationally representative their 50 older. Methods Data from 6,336 participants Irish Longitudinal Study Ageing...
Abstract Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data. Unfortunately, measurements for individual CpGs can be surprisingly unreliable due to technical noise, and this may limit the utility of epigenetic clocks. We report that noise produces deviations up 3 9 years between replicates six major The elimination low-reliability does not ameliorate issue. Here, we present a novel computational multi-step solution address involving performing principal...
Abstract Aging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention, without need for decade-spanning trials, by acting as surrogate endpoints. Prior testing whether may be useful endpoints, it is first necessary determine they are responsive interventions that target aging. Epigenetic clocks based on DNA methylation with prognostic value many outcomes. Many individual studies beginning explore epigenetic interventions. However, diversity both...
Illness anxiety disorder (IAD, formerly hypochondriasis) is characterized by preoccupation with fear of serious illness despite medical reassurance. IAD common, debilitating, challenging to treat, and results in high healthcare utilization. Outpatient management because patients can compulsively seek reassurance from numerous providers, which interferes learning more productive coping skills. We present the case a woman severe who presented emergency room increasing frequency over several...