Extracellular microRNAs associated with psychiatric symptoms in the Normative Aging Study.

Earlier studies have revealed microRNAs (miRNAs) as potential biomarkers for neurological conditions, however, such evidence on psychiatric outcomes is limited. We utilized the Normative Aging Study (NAS) cohort to investigate the associations between extracellular miRNAs (ex-miRNA) and psychiatric symptoms among a group of older male adults, along with the targeted genes and biological pathways. We studied 569 participants with miRNA profile primarily measured in extracellular vesicles isolated from plasma, and psychiatric symptoms reported over 1996-2014 with repeated measures.

The association between toenail metals and extracellular MicroRNAs (ex-miRNAs) among the participants of the Normative Aging study (NAS).

Background: Mechanistic studies of the effects of environmental risk factors have been exploring the potential role of microRNA(miRNAs) as a possible pathway to clinical disease. In this study we examine whether levels of toenail metals are associated with changes in extracellular miRNA(ex-miRNA) expression.

Methods: We used data derived from the Normative Aging Study from 1996 to 2014 to conduct our analyses.

Annual space weather fluctuations and telomere length dynamics in a longitudinal cohort of older men: the Normative Aging Study.

Background: Space weather has been associated with increased risk of cardiovascular diseases in space and flight crew. However, limited research has focused on the ground population, particularly among the elderly who are vulnerable to aging-related diseases.

Objective: We evaluated the association between space weather alterations and biological aging using leukocyte telomere length as a biomarker in healthy elderly men.

Psychological Stress and Epigenetic Aging in Older Men: The VA Normative Aging Study.

Psychological stress remains an important risk factor for morbidity and mortality throughout the life course. However, there have been counterintuitive findings reported in previous studies of older persons that examine the relationships of perceived psychological stress with DNA methylation-based markers of aging, which also serve as predictors of morbidity and mortality (epigenetic age/clocks). We aimed to replicate and expand findings from existing work by examining relationships of self-reported stress with nine epigenetic clocks: Hannum, Horvath, Intrinsic, Extrinsic, SkinBloodClock, PhenoAge, GrimAge, DNAm Telomere Length, and Pace of Aging.

Metabolomics and Self-Reported Depression, Anxiety, and Phobic Symptoms in the VA Normative Aging Study.

Traditional approaches to understanding metabolomics in mental illness have focused on investigating a single disorder or comparisons between diagnoses, but a growing body of evidence suggests substantial mechanistic overlap in mental disorders that could be reflected by the metabolome. In this study, we investigated associations between global plasma metabolites and abnormal scores on the depression, anxiety, and phobic anxiety subscales of the Brief Symptom Inventory (BSI) among 405 older males who participated in the Normative Aging Study (NAS). Our analysis revealed overlapping and distinct metabolites associated with each mental health dimension subscale and four metabolites belonging to xenobiotic, carbohydrate, and amino acid classes that were consistently associated across all three symptom dimension subscales.

Intermediate and long-term exposure to air pollution and temperature and the extracellular microRNA profile of participants in the normative aging study (NAS).

Background: The molecular effects of intermediate and long-term exposure to air pollution and temperature, such as those on extracellular microRNA (ex-miRNA) are not well understood but may have clinical consequences.

Objectives: To assess the association between exposure to ambient air pollution and temperature and ex-miRNA profiles.

Methods: Our study population consisted of 734 participants in the Normative Aging Study (NAS) between 1999 and 2015.

Short-term air pollution and temperature exposure and changes in the extracellular microRNA profile of Normative Aging Study (NAS) participants.

Background: While the health effects of air pollution and temperature are widely studied, the molecular effects are poorly understood. Extracellular microRNAs (ex-miRNAs) have the potential to serve as diagnostic or prognostic biomarkers and/or to act as intercellular signaling molecules that mediate the effects of environmental exposures on health outcomes.

Methods: We examined the relationship between short-term exposure to air pollution and ambient temperature and the ex-miRNA profiles of participants in the Normative Aging Study (NAS) from 1999 to 2015.

Extracellular microRNA and cognitive function in a prospective cohort of older men: The Veterans Affairs Normative Aging Study.

Background: Aging-related cognitive decline is an early symptom of Alzheimer's disease and other dementias, and on its own can have substantial consequences on an individual's ability to perform important everyday functions. Despite increasing interest in the potential roles of extracellular microRNAs (miRNAs) in central nervous system (CNS) pathologies, there has been little research on extracellular miRNAs in early stages of cognitive decline. We leverage the longitudinal Normative Aging Study (NAS) cohort to investigate associations between plasma miRNAs and cognitive function among cognitively normal men.

Extracellular Vesicle-Encapsulated microRNAs as Novel Biomarkers of Lung Health.

Early detection of respiratory diseases is critical to facilitate delivery of disease-modifying interventions. Extracellular vesicle-enriched microRNAs (EV-miRNAs) may represent reliable markers of early lung injury. Evaluate associations of plasma EV-miRNAs with lung function.

The role of solar and geomagnetic activity in endothelial activation and inflammation in the NAS cohort.

This study investigated the associations between solar and geomagnetic activity and circulating biomarkers of systemic inflammation and endothelial activation in the Normative Aging Study (NAS) cohort. Mixed effects models with moving day averages from day 0 to day 28 were used to study the associations between solar activity (sunspot number (SSN), interplanetary magnetic field (IMF)), geomagnetic activity (planetary K index (Kp index), and various inflammatory and endothelial markers. Biomarkers included intracellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), C-reactive protein (CRP), and fibrinogen.

Predicting risk of lung function impairment and all-cause mortality using a DNA methylation-based classifier of tobacco smoke exposure.

Background: The Epigenetic Smoking Status Estimator (EpiSmokEr) predicts smoking phenotypes based on DNA methylation at 121 CpG sites.

Objective: Evaluate associations of EpiSmokEr-predicted versus self-reported smoking phenotypes with lung function and all-cause mortality in a cohort of older adults.

Methods: The prospective Normative Aging Study collected DNA methylation measurements from 1999 to 2012 with follow-up through 2016.

Solar and geomagnetic activity reduces pulmonary function and enhances particulate pollution effects.

Background: Increased solar and geomagnetic activity (SGA) may alter sympathetic nervous system activity, reduce antioxidant activity, and modulate physiochemical processes that contribute to atmospheric aerosols, all which may reduce pulmonary function.

Objectives: Investigate associations between forced expiratory volume at 1 s (FEV) and forced vital capacity (FVC) with SGA, and assess whether SGA enhances adverse effects of particulate pollution, black carbon (BC) and particulate matter ≤2.5 μm in diameter (PM).

Geomagnetic disturbances reduce heart rate variability in the Normative Aging Study.

Background: Solar and geomagnetic activity (GA) have been linked to increased cardiovascular (CVD) events. We hypothesize that heart rate variability (HRV) may be the biological mechanism between increased CVD risk and intense geomagnetic disturbances (GMD).

Methods: To evaluate the impact of GA and intense GMD on HRV in 809 elderly men [age mean 74.

Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis.

Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function.

DunedinPACE, a DNA methylation biomarker of the pace of aging.

Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020).

Short-term air pollution, cognitive performance, and nonsteroidal anti-inflammatory drug use in the Veterans Affairs Normative Aging Study.

Air pollution, especially the fine particulate matter (PM), may impair cognitive performance, but its short-term impact remains poorly understood. We investigated the short-term associations of PM with the cognitive performances of 954 white males measured as the global cognitive function (GCF) and Mini-Mental State Examination (MMSE) scores, and further explored whether taking nonsteroidal anti-inflammatory drugs (NSAIDs) could modify their relationships. Higher short-term exposure to PM demonstrated non-linear negative associations with cognitive function.

Solar Activity Is Associated With Diastolic and Systolic Blood Pressure in Elderly Adults.

Background Since solar activity and related geomagnetic disturbances modulate autonomic nervous system activity, we hypothesized that these events would be associated with blood pressure (BP). Methods and Results We studied 675 elderly men from the Normative Aging Study (Boston, MA) with 1949 BP measurements between 2000 and 2017. Mixed-effects regression models were used to investigate the association of average 1-day (ie, day of BP measurement) to 28-day interplanetary magnetic field intensity, sunspot number, and a dichotomized measure of global geomagnetic activity (K index) in 4-day increments with diastolic and systolic BP.

Metabolomic differences in lung function metrics: evidence from two cohorts.

Rationale: The biochemical mechanisms underlying lung function are incompletely understood.

Objectives: To identify and validate the plasma metabolome of lung function using two independent adult cohorts: discovery-the European Prospective Investigation into Cancer-Norfolk (EPIC-Norfolk, n=10 460) and validation-the VA Normative Aging Study (NAS) metabolomic cohort (n=437).

Methods: We ran linear regression models for 693 metabolites to identify associations with forced expiratory volume in one second (FEV) and the ratio of FEV to forced vital capacity (FEV/FVC), in EPIC-Norfolk then validated significant findings in NAS.

Associations between solar and geomagnetic activity and peripheral white blood cells in the Normative Aging Study.

It has been hypothesized that solar and geomagnetic activity can affect the function of the autonomic nervous system (ANS) and melatonin secretion, both of which may influence immune response. We investigated the association between solar geomagnetic activity and white blood cell counts in the Normative Aging Study (NAS) Cohort between 2000 and 2013. Linear mixed effects models with moving day averages ranging from 0 to 28 days were used to evaluate the effects of solar activity measures, interplanetary magnetic field (IMF), and sunspot number (SSN), and a measure of geomagnetic activity, K Index (K), on total white blood cell (WBC), neutrophil, monocytes, lymphocyte, eosinophil, and basophil concentrations.

Short-term exposure to PM components and renal health: Findings from the Veterans Affairs Normative Aging Study.

There is little evidence on the short-term impact of fine particulate matter (PM) on renal health, and the potential interactions and various influences of PM components on renal health have not been examined. We investigated whether short-term (≤28 days) ambient PM and 15 PM components were associated with serum uric acid (SUA), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and odds of incident chronic kidney disease (CKD) using both mixed-effect and Bayesian kernel machine regression (BKMR) models in the Normative Aging Study. This analysis included 2466 study visits from 808 older males enrolled during 1998-2016 with available data.

Metabolomic signatures of the short-term exposure to air pollution and temperature.

Background: Short-term exposures to air pollution and temperature have been reported to be associated with inflammation and oxidative stress. However, mechanistic understanding of the affected metabolic pathways is still lacking and literature on the short-term exposure of air-pollution on the metabolome is limited.

Objectives: We aimed to determine changes in the plasma metabolome and associated metabolic pathways related to short-term exposure to outdoor air pollution and temperature.