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. The majority of research focuses on identifying differences in EVs when comparing disease states and matched controls. Here, we analyzed circulating plasma EVs in a cross-sectional and longitudinal study in order to address age-related changes in community-dwelling individuals. We found that EV concentration decreases with advancing age. Furthermore, EVs from older individuals were more readily internalized by B cells and increased MHC-II expression on monocytes compared with EVs from younger individuals, indicating that the decreased concentration of EVs with age may be due in part to increased internalization. EVs activated both monocytes and B cells, and activation of B cells by LPS enhanced EV internalization. We also report a relative stability of EV concentration and protein amount in individual subjects over time. Our data provide important information towards establishing a profile of EVs with human age, which will further aid in the development of EV-based diagnostics for aging and age-related diseases.

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. Here, we designed cross-sectional and longitudinal cohorts of euglycemic participants and participants with prediabetes or diabetes. Individuals with diabetes had significantly higher levels of EVs in their circulation than euglycemic control participants. Using a cell-specific EV assay, we identified that levels of erythrocyte-derived EVs are higher with diabetes. We found that insulin resistance increases EV secretion. Furthermore, the levels of insulin signaling proteins were altered in EVs from individuals with high levels of insulin resistance and β-cell dysfunction. Moreover, EVs from individuals with diabetes were preferentially internalized by circulating leukocytes. Cytokine levels in the media and in EVs were higher from monocytes incubated with diabetic EVs. Microarray of these leukocytes revealed altered gene expression pathways related to cell survival, oxidative stress, and immune function. Collectively, these results suggest that insulin resistance increases the secretion of EVs, which are preferentially internalized by leukocytes, and alters leukocyte function.

Two hypotheses have been proposed to explain the abundance-occupancy relationship (AOR) in parasites. The niche breadth hypothesis suggests that host generalists are more abundant and efficient at colonizing different host communities than specialists. The trade-off hypothesis argues that host specialists achieve high density across their hosts' ranges, whereas generalists incur the high cost of adaptation to diverse immuno-defence systems. We tested these hypotheses using 386 haemosporidian cytochrome-b lineages (1894 sequences) recovered from 2318 birds of 103 species sampled in NW Africa, NW Iberia, W Greater Caucasus and Transcaucasia. The number of regions occupied by lineages was associated with their frequency suggesting the presence of AOR in avian Haemosporidia. However, neither hypothesis provided a better explanation for the AOR. Although the host generalist Plasmodium SGS1 was over three times more abundant than other widespread lineages, both host specialists and generalists were successful in colonizing all study regions and achieved high overall prevalence.

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. Here, we report that a portion of ccf‐mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30–64 years cross‐sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV‐derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age‐dependent manner.

BackgroundBody mass index (BMI) based on self-reported height and weight has been criticized as being biased because of an observed tendency for overweight and obese people to overestimate height and underestimate weight, resulting in higher misclassification for these groups. We examined the validity of BMI based on self-reported values in a sample of Norwegian women aged 44–64 years.MethodsThe study sample of 1,837 participants in the Norwegian Women and Cancer study self-reported height and weight, and then, within 1 year, either self-reported anthropometric again, or were measured by medical staff. Demographic and anthropometric were compared using t-tests and chi-square tests of independence. Misclassification of BMI categories was assessed by weighted Cohen’s kappa and Bland–Altman plot.ResultsOn average, the two measurements were taken 8 months apart, and self-reported weight increased by 0.6 kg (P<0.05), and BMI by 0.2 kg/m2 (P<0.05). The distribution of BMI categories did not differ between self-reported and measured values. There was substantial agreement between self-reported values and those measured by medical staff (weighted kappa 0.73). Under-reporting resulting in misclassification of BMI category was most common among overweight women (36%), but the highest proportion of extreme under-reporting was found in obese women (18% outside the 95% limits of agreement). The cumulative distribution curves for the measured and self-reported values closely followed each other, but measurements by medical staff were shifted slightly toward higher BMI values.ConclusionWhile there was substantial agreement between self-reported and measured BMI values, there was small but statistically significant under-reporting of weight and thus self-reported BMI. The tendency to under-report was largest among overweight women, while the largest degree of under-reporting was found in the obese group. Self-reported weight and height provide a valid ranking of BMI for middle-aged Norwegian women.

Mortality rates in the United States vary based on race, individual economic status and neighborhood. Correlations among these variables in most urban areas have limited what conclusions can be drawn from existing research. Our study employs a unique factorial design of race, sex, age and individual poverty status, measuring time to death as an objective measure of health, and including both neighborhood economic status and income inequality for a sample of middle-aged urban-dwelling adults (N = 3675). At enrollment, African American and White participants lived in 46 unique census tracts in Baltimore, Maryland, which varied in neighborhood economic status and degree of income inequality. A Cox regression model for 9-year mortality identified a three-way interaction among sex, race and individual poverty status (p = 0.03), with African American men living below poverty having the highest mortality. Neighborhood economic status, whether measured by a composite index or simply median household income, was negatively associated with overall mortality (p<0.001). Neighborhood income inequality was associated with mortality through an interaction with individual poverty status (p = 0.04). While racial and economic disparities in mortality are well known, this study suggests that several social conditions associated with health may unequally affect African American men in poverty in the United States. Beyond these individual factors are the influences of neighborhood economic status and income inequality, which may be affected by a history of residential segregation. The significant association of neighborhood economic status and income inequality with mortality beyond the synergistic combination of sex, race and individual poverty status suggests the long-term importance of small area influence on overall mortality.

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. Results We measured genome-wide DNA methylation (866,836 CpGs) using the Illumina MethylationEPIC BeadChip in blood DNA extracted from 487 middle-aged AA ( N = 244) and white ( N = 243), men ( N = 248), and women ( N = 239). The mean (sd) age was 48.4 (8.8) in AA and 49.0 (8.7) in whites ( p = 0.48). We identified 4930 significantly associated aDMPs in AAs and 469 in whites. Of these, 75.6% and 53.1% were novel, largely driven by the increased number of measured CpGs in the EPIC array, in AA and whites, respectively. AAs had more age-associated DNAm changes than whites in genes implicated in age-related diseases and cellular pathways involved in growth and development. We assessed three epigenetic age acceleration measures (universal, intrinsic, and extrinsic). AAs had a significantly slower extrinsic aging compared to whites. Furthermore, compared to AA women, both AA and white men had faster aging in the universal age acceleration measure (+ 2.04 and + 1.24 years, respectively, p < 0.05). Conclusions AAs have more wide-spread methylation changes than whites. Race and sex interact to underlie biological age acceleration suggesting altered DNA methylation patterns may be important in age-associated health disparities. Electronic supplementary material The online version of this article (10.1186/s13148-019-0722-1) contains supplementary material, which is available to authorized users.

Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.