Validating 8 Area-Based Measures of Social Risk for Predicting Health and Mortality.

Importance: Area-based measures of social risk are increasingly being used in policy applications in the US. While several have been demonstrated to be predictive of health and mortality in the general population, there is a need to identify area-based measures that are most reliable for policy applications, including measures that are associated with health and mortality consistently across subpopulations.

Objective: To compare the relative strength with which area and individual social risk measures are correlated with health outcomes and mortality, and the extent to which these associations are consistent across race, ethnicity, rurality, age, and gender.

Dietary Fatty Acids and Epigenetic Aging in US Adults: Results from the National Health and Nutrition Examination Survey.

Fatty acids are involved in disease risk and aging processes. In the US National Health and Nutrition Examination Survey (1999-2002), we tested for associations of total, saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and subtypes of dietary fatty acids with DNA methylation-based aging biomarkers, adjusting for age, BMI, total energy intake, and sociodemographic and behavioral factors (N=2,260). Higher SFA and MUFA were associated with greater GrimAge2, an aging biomarker of mortality; PUFA was associated with lower Horvath1, Hannum, and PhenoAge (<0.

Racial and ethnic differences in epigenetic aging: The National Health and Nutrition Examination Survey, 1999-2002.

Background: Accelerated biological aging due to differences in socially patterned exposures has been proposed as a mechanism underlying racial and ethnic disparities in morbidity and mortality. Research exploring this hypothesis has been limited by a lack of consensus regarding the measurement of biological aging.

Objective: The goal of this study is to examine self-reported race and ethnicity as a predictor of 13 measures of epigenetic aging.

Longitudinal Epigenetic Aging in Pregnancy and Associations With Adverse Outcomes.

Objective: To understand the relationship between pregnancy and epigenetic aging estimated by DNA methylation "clocks," which offers a molecular measure of biologic aging.

Methods: This was a prospective cohort study of nulliparous women (age 18-50 years) seeking obstetric (pregnant 10-14 weeks) or gynecologic (nonpregnant) care in 2020-2021. Blood was collected at enrollment (time 1) and postpartum day 1 (pregnant, time 2) or 7 months later (nonpregnant, time 2).

One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: results from the cross-sectional National Health and Nutrition Examination Survey 1999-2002.

Background: One-carbon metabolism (OCM), a biochemical pathway dependent on micronutrients including B vitamins, plays an essential role in aging-related physiological processes. DNA methylation-based aging biomarkers may be influenced by OCM.

Objectives: This study investigated associations of OCM-related biomarkers with epigenetic aging biomarkers in the cross-sectional National Health and Nutrition Examination Survey (1999-2002).

Sensory impairments and epigenetic aging: insights from self-rated hearing and vision in United States adults.

Sensory impairments are common with aging, but studies examining the relationships of these impairments with DNA methylation-based biomarkers of aging, strong predictors of morbidity and mortality, remain sparse. We investigated whether subjective measures of sensory impairment are associated with epigenetic age biomarkers. We conducted a cross-sectional analysis in a representative sample of 2344 U.

Health insurance and epigenetic aging: Trends in a United States adult population.

Background: Health insurance plays an important role in reducing morbidity and mortality. Still, there is limited data examining the relationships of health insurance with biomarkers of aging that reflect morbidity and mortality risk.

Methods: We conducted a cross-sectional study of United States adults using data from the National Health and Nutrition Examination Survey (NHANES) to examine the relationships of health insurance with seven DNA methylation-based biomarkers of aging (epigenetic age): HannumAge, HorvathAge, SkinBloodAge, PhenoAge, GrimAge2, DNAm Telomere Length, and DunedinPoAm.

Associations of epigenetic aging with self-rated health, access to care, and healthcare utilization in a representative sample of United States adults.

Background: Health status is closely linked to both healthcare access and utilization. While previous research has identified associations between health status and DNA methylation-based biomarkers of aging (epigenetic aging), studies exploring these relationships in the context of healthcare access and utilization remain limited. To address this gap, we analyzed cross-sectional associations in a representative sample of 2,343 U.

Influence of race, ethnicity, and sex on the performance of epigenetic predictors of phenotypic traits.

Background: DNA methylation-based predictors of phenotypic traits including leukocyte proportions, smoking activity, biological aging, and circulating levels of plasma proteins are widely used as biomarkers in public health research. However, limited racial and ethnic diversity of research participants is an ongoing issue for epigenetics research, and the potential downstream impacts of limited diversity in training samples on the performance of epigenetic predictors remains poorly understood. We examined the performance of epigenetic predictors of chronological age (also known as epigenetic clocks), telomere length, cell proportions, and plasma proteins within a diverse sample of adult NHANES participants during the 1999-2000 and 2001-2002 survey cycles, both overall and stratified by self-reported race/ethnicity and sex.

Comparing Veteran and Nonveteran Epigenetic Aging in a Representative Sample of United States Adults.

Introduction: Military service can significantly impact human health, with research showing that veterans experience higher mortality rates than the general population. However, limited data exist on the relationships of veteran status with biomarkers of aging that may precede clinical illness and mortality.

Methods: Using survey-design weighted generalized linear regression models, we examined the cross-sectional relationship of self-reported veteran status with DNA methylation (DNAm)-based biomarkers of aging (epigenetic age) in a representative sample of 2344 U.

Immigrant status and citizenship relationships with epigenetic aging in a representative sample of United States adults.

Background: Immigrant status and citizenship influence health and well-being, yet their associations with DNA methylation (DNAm)-based biomarkers of aging - key predictors of healthspan and lifespan, also known as epigenetic aging - remain underexplored.

Methods: Using a representative sample of 2,336 United States (U.S.

Timing of menarche and menopause and epigenetic aging among U.S. adults: results from the National Health and Nutrition Examination Survey 1999-2002.

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N = 1,033) and menopause (N = 658) with epigenetic aging in a nationally representative sample of women ≥ 50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation ( = - 0.

Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey.

Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging. However, research on the influence of environmental exposures on epigenetic aging has largely been limited to a small number of chemicals and specific populations. We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging.

Incorporating area-level social drivers of health in predictive algorithms using electronic health record data.

Objectives: The inclusion of social drivers of health (SDOH) into predictive algorithms of health outcomes has potential for improving algorithm interpretation, performance, generalizability, and transportability. However, there are limitations in the availability, understanding, and quality of SDOH variables, as well as a lack of guidance on how to incorporate them into algorithms when appropriate to do so. As such, few published algorithms include SDOH, and there is substantial methodological variability among those that do.

One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: Results from National Health and Nutrition Examination Survey (NHANES) 1999-2002.

Background: One-carbon metabolism (OCM), a biochemical pathway dependent on micronutrients including folate and vitamin B12, plays an essential role in aging-related physiological processes. DNA methylation-based aging biomarkers may be influenced by OCM.

Objective: This study investigated associations of OCM-related biomarkers with epigenetic aging biomarkers in the National Health and Nutrition Examination Survey (NHANES).

Timing of Menarche and Menopause and Epigenetic Aging among U.S. Adults: Results from the National Health and Nutrition Examination Survey 1999-2002.

Reproductive aging, including timing of menarche and menopause, influences long-term morbidity and mortality in women, yet underlying biological mechanisms remain poorly understood. Using DNA methylation-based biomarkers, we assessed associations of age at menarche (N=1,033) and menopause (N=658) with epigenetic aging in a nationally representative sample of women ≥50 years. Later age at menopause was associated with lower GrimAge epigenetic age deviation ( = -0.

Linking national primary care electronic health records to individual records from the U.S. Census Bureau's American Community Survey: evaluating the likelihood of linkage based on patient health.

Objectives: To evaluate the likelihood of linking electronic health records (EHRs) to restricted individual-level American Community Survey (ACS) data based on patient health condition.

Materials And Methods: Electronic health records (2019-2021) are derived from a primary care registry collected by the American Board of Family Medicine. These data were assigned anonymized person-level identifiers (Protected Identification Keys [PIKs]) at the U.

Sex-Specific Associations between Prenatal Exposure to Bisphenols and Phthalates and Infant Epigenetic Age Acceleration.

We examined whether prenatal exposure to two classes of endocrine-disrupting chemicals (EDCs) was associated with infant epigenetic age acceleration (EAA), a DNA methylation biomarker of aging. Participants included 224 maternal-infant pairs from a Canadian pregnancy cohort study. Two bisphenols and 12 phthalate metabolites were measured in maternal second trimester urines.

Association between Maternal Perinatal Stress and Depression on Infant DNA Methylation in the First Year of Life.

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown.

Sex differences in epigenetic age in Mediterranean high longevity regions.

Sex differences in aging manifest in disparities in disease prevalence, physical health, and lifespan, where women tend to have greater longevity relative to men. However, in the Mediterranean Blue Zones of Sardinia (Italy) and Ikaria (Greece) are regions of centenarian abundance, male-female centenarian ratios are approximately one, diverging from the typical trend and making these useful regions in which to study sex differences of the oldest old. Additionally, these regions can be investigated as examples of healthy aging relative to other populations.

Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection.

Importance: Very preterm neonates (24-32 weeks' gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population.

Objectives: To characterize the pediatric buccal epigenetic (PedBE) clock-a recently developed tool to measure biological aging-among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age.

Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways.

Parkinson's disease (PD) is a neurological disorder with complex interindividual etiology that is becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation of PD pathways. Here, we report genome-wide DNA methylation and hydroxymethylation alterations associated with overexpression of two PD-linked alpha-synuclein variants (wild-type and A30P) in LUHMES cells differentiated to dopaminergic neurons.

In-utero exposure to indoor air pollution or tobacco smoke and cognitive development in a South African birth cohort study.

Background And Aims: There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10 μm, PM) and tobacco smoke with neurodevelopment and 2) to determine whether these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA).

Methylation risk scores for childhood aeroallergen sensitization: Results from the LISA birth cohort.

Background: Epigenomic (e.g., DNA methylation [DNAm]) changes have been hypothesized as intermediate step linking environmental exposures with allergic disease.