Abstract
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.
Highlights
Extracellular vesicles (EVs) are nano-sized (30–400 nm) membranous vesicles that are secreted by a variety of cell types into the circulation and other bodily fluids
In order to examine the relationship between age and extracellular vesicles (EVs) circulating in the blood, we isolated plasma EVs from a sub-cohort of the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, which is a longitudinal, epidemiologic study of aging
We chose this method after careful consideration and evaluation, since differential ultracentrifugation procedures were not feasible for a large number of samples, and because this method provided more reproducible data than either differential ultracentrifugation or size exclusion columns (Fig. 1A)
Summary
Extracellular vesicles (EVs) are nano-sized (30–400 nm) membranous vesicles that are secreted by a variety of cell types into the circulation and other bodily fluids. We analyzed EVs in a cross-sectional and longitudinal study and found an age-related decrease in EVs concentration and altered uptake by immune cells.
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