A5051398269- Epigenetics and DNA Methylation
- Genetics, Aging, and Longevity in Model Organisms
- Health, Environment, Cognitive Aging
- Birth, Development, and Health
- Health disparities and outcomes
- Frailty in Older Adults
- Intergenerational Family Dynamics and Caregiving
- Genetics and Neurodevelopmental Disorders
- Nutrition and Health in Aging
- Telomeres, Telomerase, and Senescence
- Genetic Associations and Epidemiology
- Diet and metabolism studies
- Aging and Gerontology Research
- Genetic Syndromes and Imprinting
- Genomics and Chromatin Dynamics
- Dementia and Cognitive Impairment Research
- Bioinformatics and Genomic Networks
- Identity, Memory, and Therapy
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Air Quality and Health Impacts
- Nutrition, Genetics, and Disease
- Dietary Effects on Health
- Insurance, Mortality, Demography, Risk Management
- Resilience and Mental Health
Yale University
2017-2025
Fleet Science Center
2022-2024
Altos Labs
2022-2024
University of California, Los Angeles
2015-2018
University of Southern California
2012-2018
VA Palo Alto Health Care System
2016
Identifying reliable biomarkers of aging is a major goal in geroscience.While the first generation epigenetic were developed using chronological age as surrogate for biological age, we hypothesized that incorporation composite clinical measures phenotypic capture differences lifespan and healthspan may identify novel CpGs facilitate development more powerful biomarker
Antiaging therapies show promise in model organism research. Translation to humans is needed address the challenges of an aging global population. Interventions slow human will need be applied still-young individuals. However, most research examines older adults, many with chronic disease. As a result, little known about young humans. We studied 954 humans, Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades life....
Biological age (BA) is useful for examining differences in aging rates.Nevertheless, little consensus exists regarding optimal methods calculating BA.The aim of this study to compare the predictive ability five BA algorithms.The sample included 9,389 persons, aged 30-75 years, from National Health and Nutrition Examination Survey III.During 18-year follow-up, 1,843 deaths were counted.Each algorithm was compared with chronological on basis sensitivity strength association mortality.Results...
Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence cardio-metabolic disease such as: (1) women consistently exhibiting lower than men despite having higher levels morbidity; (2) racial/ethnic groups different even after adjusting for socioeconomic differences; (3) black/white cross-over effect in late adulthood; (4) Hispanics United States a longer life expectancy Caucasians burden traditional risk...
Aging | doi:10.18632/aging.101168. Austin Quach, Morgan E. Levine, Toshiko Tanaka, Ake T. Lu, Brian H. Chen, Luigi Ferrucci, Beate Ritz, Stefania Bandinelli, Marian L. Neuhouser, Jeannette M. Beasley, Linda Snetselaar, Robert B. Wallace, Philip S. Tsao, Devin Absher, Themistocles Assimes, James D. Stewart, Yun Li, Lifang Hou, Andrea A. Baccarelli, Eric Whitsel, Steve Horvath
Significance Within an evolutionary framework, aging and reproduction are intrinsically linked. Although both laboratory epidemiological studies have observed associations between the timing of reproductive senescence longevity, it is not yet known whether differences in age menopause reflected biomarkers aging. Using our recently developed biomarker aging, “epigenetic clock,” we examined at associated with epigenetic blood, saliva, buccal epithelium. This a definitive study that shows...
There is an urgent need to develop molecular biomarkers of brain age in order advance our understanding related neurodegeneration. Recently, we developed a highly accurate epigenetic biomarker tissue (known as clock) which based on DNA methylation levels. Here use n=700 dorsolateral prefrontal cortex (DLPFC) samples from Caucasian subjects the Religious Order Study and Rush Memory Aging Project examine association between Alzheimerâs disease (AD) cognitive decline, AD neuropathological...
Background A person's rate of aging has important implications for his/her risk death and disease; thus, quantifying using observable characteristics applications clinical, basic, observational research. Based on routine clinical chemistry biomarkers, we previously developed a novel measure, Phenotypic Age, representing the expected age within population that corresponds to estimated mortality risk. The aim this study was assess its applicability differentiating variety health outcomes...
The geroscience hypothesis posits that therapies to slow biological processes of aging can prevent disease and extend healthy years life. To test such "geroprotective" in humans, outcome measures are needed assess extension disease-free life span. This need has spurred development different methods quantify aging. But have not been systematically compared the same humans. We implemented 7 using repeated-measures physiological genomic data 964 middle-aged humans Dunedin Study (New Zealand;...
Lung cancer is considered an age-associated disease, whose progression in part due to accumulation of genomic instability as well age-related decline system integrity and function. Thus even among individuals exposed high levels genotoxic carcinogens, such those found cigarette smoke, lung susceptibility may vary a function individual differences the rate biological aging. We recently developed highly accurate candidate biomarker aging based on DNA methylation (DNAm) levels, which prove...
Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different processes. We utilize multi-omics data from diverse human tissue/cells identify shared features across eleven clocks. Despite the striking lack of overlap CpGs, analysis suggested five (Horvath1, Horvath2, Levine, Hannum, and Lin) share...
Abstract DNA methylation age is an accurate biomarker of chronological and predicts lifespan, but its underlying molecular mechanisms are unknown. In this genome-wide association study 9907 individuals, we find gene variants mapping to five loci associated with intrinsic epigenetic acceleration (IEAA) in three extrinsic (EEAA). Mendelian randomization analysis suggests causal influences menarche menopause on IEAA lipoproteins EEAA. Variants longer leukocyte telomere length (LTL) the...
Abstract Background Many DNA methylation-based indicators have been developed as summary measures of epigenetic aging. We examine the associations between 13 clocks, including 4 second generation well links clocks to social, demographic, and behavioral factors known be related health outcomes: sex, race/ethnicity, socioeconomic status, obesity, lifetime smoking pack-years. Methods The Health Retirement Study is data source which a nationally representative sample Americans over age 50....
Biomarkers developed from DNA methylation (DNAm) data are of growing interest as predictors health outcomes and mortality in older populations. However, it is unknown how epigenetic aging fits within the context known socioeconomic behavioral associations with aging-related a large, population-based, diverse sample. This study uses representative, panel US adults to examine relationship between DNAm-based age acceleration measures prediction cross-sectional longitudinal mortality. We whether...
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....
Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on single haploid reference genome. Here, we present the EN-TEx resource 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating catalog >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes less conserved...
Age associated increases in visceral adiposity and decreases muscle mass (sarcopenia) have been shown to contribute disability late life. Furthermore, there is evidence that obesity-related physiological states, such as insulin resistance systemic inflammation, may exacerbate physical functioning problems. Both conditions prompt hypercatabolism impair the anabolic effect of muscles, ultimately stimulating protein breakdown suppressing synthesis. This cross-sectional study investigates...