Extracellular vesicle mitochondrial DNA levels are associated with race and mitochondrial DNA haplogroup.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) acts as a damage-associated molecular pattern molecule and may be cargo within extracellular vesicles (EVs). ccf-mtDNA and select mitochondrial DNA (mtDNA) haplogroups are associated with cardiovascular disease. We hypothesized that ccf-mtDNA and plasma EV mtDNA would be associated with hypertension, sex, self-identified race, and mtDNA haplogroup ancestry.

Pro-Inflammatory Diets Are Associated with Frailty in an Urban Middle-Aged African American and White Cohort.

Diet quality is a modifiable risk factor for frailty, but research on the association of frailty with dietary inflammatory potential is limited. The objective was to determine associations between diet quality assessed by the dietary inflammatory index (DII) with frailty status over time. Participants with both dietary and frailty data from the longitudinal Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used ( = 2901, 43.

Inflammatory proteins are associated with mortality in a middle-aged diverse cohort.

Background: Recent data indicate a decline in overall longevity in the United States. Even prior to the COVID-19 pandemic, an increase in midlife mortality rates had been reported. Life expectancy disparities have persisted in the United States for racial and ethnic groups and for individuals living at low socioeconomic status.

Diet Quality Trajectories over Adulthood in a Biracial Urban Sample from the Healthy Aging in Neighborhoods of Diversity across the Life Span Study.

Limited investigation has been done on diet quality trajectories over adulthood. The main study objectives were to determine the diet quality group trajectories (GTs) over time and to detect changes in a socio-economically and racially diverse middle-aged cohort. Data from three waves of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study were used to determine diet quality with group-based trajectory modeling (GBTM).

Frailty, sex, and poverty are associated with DNA damage and repair in frail, middle-aged urban adults.

Frailty is an age-related syndrome characterized by reduced recovery from stressors and increased risks of morbidity and mortality. Although frailty is usually studied in those over 65 years, our previous work showed that frailty is both present and a risk factor for premature mortality in midlife. We identified altered gene expression patterns and biological pathways associated with inflammation in frailty.

Association of Race and Poverty Status With DNA Methylation-Based Age.

Importance: The Dunedin Pace of Aging Calculated From the Epigenome (DunedinPACE) measure is a newly constructed DNA methylation (DNAm) biomarker associated with morbidity, mortality, and adverse childhood experiences in several cohorts with European ancestry. However, there are few studies of the DunedinPACE measure among socioeconomically and racially diverse cohorts with longitudinal assessments.

Objective: To investigate the association of race and poverty status with DunedinPACE scores in a socioeconomically diverse middle-aged cohort of African American and White participants.

Plasma gelsolin levels are associated with diabetes, sex, race, and poverty.

Background: The growing epidemic of the inflammation-related metabolic disease, type 2 diabetes mellitus, presents a challenge to improve our understanding of potential mechanisms or biomarkers to prevent or better control this age-associated disease. A gelsolin isoform is secreted into the plasma as part of the extracellular actin scavenger system which serves a protective role by digesting and removing actin filaments released from damaged cells. Recent data indicate a role for decreased plasma gelsolin (pGSN) levels as a biomarker of inflammatory conditions.

Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals.

Background: Frailty, a clinical syndrome commencing at midlife, is a risk for morbidity and mortality. Little is known about the factors that contribute to the chronic inflammatory state associated with frailty. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released into the circulation and are mediators of intercellular communication.

Association of extracellular vesicle inflammatory proteins and mortality.

Even before the COVID-19 pandemic declines in life expectancy in the United States were attributed to increased mortality rates in midlife adults across racial and ethnic groups, indicating a need for markers to identify individuals at risk for early mortality. Extracellular vesicles (EVs) are small, lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids. Given their role as intercellular communicators and potential biomarkers of disease, we explored whether circulating EVs may be markers of mortality in a prospective, racially, and socioeconomically diverse middle-aged cohort.

Sex-specific transcriptome differences in a middle-aged frailty cohort.

Background: Frailty is a clinical syndrome described as reduced physiological reserve and increased vulnerability. Typically examined in older adults, recent work shows frailty occurs in middle-aged individuals and is associated with increased mortality. Previous investigation of global transcriptome changes in a middle-aged cohort from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study demonstrated inflammatory genes and pathways were significantly altered by frailty status and race.

APOE gene region methylation is associated with cognitive performance in middle-aged urban adults.

Apolipoprotein (APOE) ε4 allele is a strong risk factor for Alzheimer's disease (AD) and cognitive decline. Epigenetic modifications such as DNA methylation (DNAm) play a central role in cognition. This study sought to identify DNAm sites in the APOE genomic region associated with cognitive performance in a racially diverse middle-aged cohort (n = 411).

Healthy Behaviors Associated with Changes in Mental and Physical Strength in Urban African American and White Adults.

Over time, adherence to healthy behaviors may improve physical and mental strength which is essential for successful aging. A plausible mechanism is the reduction of inflammation. Research on the association of risky health behaviors on change in strength with age is limited.

Mitochondrial DNA in extracellular vesicles declines with age.

The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell-free mtDNA (ccf-mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30-400 nm), lipid-bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems.

Association between GDF15, poverty and mortality in urban middle-aged African American and white adults.

Mortality disparities are influenced by race and poverty. There is limited information about whether poverty influences biologic markers of mortality risk. Emerging data suggests that growth differentiation factor 15 (GDF15) is associated with mortality; however, the interplay between GDF15, sociodemographic factors and mortality is not known.

Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration.

Background: Inflammation-related atherosclerotic peripheral vascular disease is a major end organ complication of diabetes mellitus that results in devastating morbidity and mortality. Extracellular vesicles (EVs) are nano-sized particles that contain molecular cargo and circulate in the blood. Here, we examined EV protein cargo from diabetic individuals and whether these EVs cause functional changes in endothelial cells.

Association of Extracellular Vesicle Protein Cargo with Race and Clinical Markers of Mortality.

Differential mortality rates remain a significant health disparity in the United States, suggesting the need to investigate novel potential molecular markers associated with mortality. Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, are lipid-bound vesicles secreted by cells into the circulation. EVs mediate intercellular communication by shuttling functional signaling molecules as cargo.

Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS.

Cross-Sectional Associations of Neighborhood Perception, Physical Activity, and Sedentary Time in Community-Dwelling, Socioeconomically Diverse Adults.

Little is known about the role of perceived neighborhood environment as a determinant of physical activity (PA) and sedentary time (ST) in understanding obesity-related health behaviors. We focus on a biracial, socioeconomically diverse population using objectively measured ST, which is under-represented in the literature. We examined the association between self-reported neighborhood perception (Likert-scale questions), PA using the Baecke questionnaire, and both non-sedentary time and ST using accelerometry from wave 4 of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study ( = 2,167).

Novel age-associated DNA methylation changes and epigenetic age acceleration in middle-aged African Americans and whites.

Background: African Americans (AAs) experience premature chronic health outcomes and longevity disparities consistent with an accelerated aging phenotype. DNA methylation (DNAm) levels at specific CpG positions are hallmarks of aging evidenced by the presence of age-associated differentially methylated CpG positions (aDMPs) that are the basis for the epigenetic clock for measuring biological age acceleration. Since DNAm has not been widely studied among non-European populations, we examined the association between DNAm and chronological age in AAs and whites, and the association between race, poverty, sex, and epigenetic age acceleration.

Frailty in middle age is associated with frailty status and race-specific changes to the transcriptome.

Frailty is an aging-associated syndrome resulting from diminished capacity to respond to stressors and is a significant risk factor for disability and mortality. Although frailty is usually studied in old age, it is present in mid-life. Given the increases in mortality statistics among middle-aged Americans, understanding molecular drivers of frailty in a younger, diverse cohort may facilitate identifying pathways for early intervention.

Altered Extracellular Vesicle Concentration, Cargo, and Function in Diabetes.

Type 2 diabetes is a chronic age-associated degenerative metabolic disease that reflects relative insulin deficiency and resistance. Extracellular vesicles (EVs) (exosomes, microvesicles, and apoptotic bodies) are small (30-400 nm) lipid-bound vesicles capable of shuttling functional proteins, nucleic acids, and lipids as part of intercellular communication systems. Recent studies in mouse models and in cell culture suggest that EVs may modulate insulin signaling.

Epigenome-wide association study of adiposity and future risk of obesity-related diseases.

Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.

Methods: DNA methylation profiles (Illumina Infinium HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework.

Frailty in a racially and socioeconomically diverse sample of middle-aged Americans in Baltimore.

Frailty is a risk factor for disability and mortality, and is more prevalent among African American (AA) elderly than whites. We examine frailty in middle-aged racially and economically diverse adults, and investigate how race, poverty and frailty are associated with mortality. Data were from 2541 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study in Baltimore, Maryland; 35-64 years old at initial assessment (56% women; 58% AA).

Age-Related Changes in Plasma Extracellular Vesicle Characteristics and Internalization by Leukocytes.

Cells release lipid-bound extracellular vesicles (EVs; exosomes, microvesicles and apoptotic bodies) containing proteins, lipids and RNAs into the circulation. Vesicles mediate intercellular communication between both neighboring and distant cells. There is substantial interest in using EVs as biomarkers for age-related diseases including cancer, and neurodegenerative, metabolic and cardiovascular diseases.