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

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.

Blood neuron-derived exosomes as biomarkers of cognitive impairment in HIV

“…It will be important to investigate concentration and content changes in exosomes in age-related pathologies. A recent report showed that the concentration of extracellular vesicles (EV) from normal subjects decreased with aging [49]. Our data from controls showed no correlation; however, this discrepancy may due to the age of our controls, which spanned a relatively narrow range of middle age.…”

“…Despite the increased concentration, we observed a significant decrease in HMGB1 protein and trending decrease in NF-L and Aβ with age. A recent report on aging found that EV content might change with normal aging [49]. While the function of HMGB1 in brain is little understood, it appears that it can regulate DNA repair mechanisms.…”

Extracellular vesicles and aging

“…In a recent study, the levels of circulating EVs in plasma were shown to decrease in a cross-sectional and longitudinal study. Here it also was demonstrated that plasma EVs from older individuals had increased MHC-II expression on monocytes and were more readily internalized by B cells (72). This uptake of the plasma EVs results in activation of not only B cells, but also monocytes (72).…”

“…Here it also was demonstrated that plasma EVs from older individuals had increased MHC-II expression on monocytes and were more readily internalized by B cells (72). This uptake of the plasma EVs results in activation of not only B cells, but also monocytes (72). Thus circulating EVs in aged individuals likely can modulate the immune response.…”

The Aging Process Alters IL-1β and CD63 Levels Differently in Extracellular Vesicles Obtained from the Plasma and Cerebrospinal Fluid

“…In accordance, lower CD63 levels were here observed in plasma. Eitan et al [28] suggested that aging-induced decrease in circulating EVs is related to an increased internalization of vesicles into cells. On the other hand, our data could indicate increases in free IL-1β instead of package into exosomes, which might indicate different biological functions.…”