Influences of age, race, and sex on extracellular vesicle characteristics

Abstract

Recent attention has focused on the use of extracellular vesicles (EVs) as biological indicators of health and disease. These small, nano-sized membrane bound vesicles are secreted from cells into the extracellular space and can be readily isolated from bodily fluids. EVs can carry various bioactive molecules as cargo including DNA, RNA, proteins, and lipids. These EVs can provide a snapshot of the cell of origin and a window of opportunity to assess normal physiological states as well as pathophysiological states. For EVs to further develop as potential biomarkers of disease, it is important to characterize whether these vesicles and their associated cargo are altered in the context of demographic factors. Here, we summarize the current literature on how demographics such as age, race, and sex affect the levels and cargo of EVs. Age and sex influence both EV cargo and concentration while race studies report differences mostly in EV protein cargo. This review also identifies areas of future research and important considerations for the clinical use of EVs as biomarkers.

Association of extracellular vesicle inflammatory proteins and mortality

“…We also reported a higher EV level of phospho-IGF-1R in women compared to men. In addition, little is known about differences in EV cargo with various demographics 35 . Here, we wanted to examine if there were differences in EV inflammatory proteins with race, sex, and poverty status.…”

“…Few studies have examined whether race influences EVs 35 . Previously, we reported that there were racial differences in EV protein cargo and found higher levels of phospho-p53, total p53, cleaved caspase 3, ERK1/2 and phospho-AKT in White individuals compared to African American individuals 25 .…”

Extracellular vesicles in atherothrombosis: From biomarkers and precision medicine to therapeutic targets

“…EVs are present in any human body fluid (plasma, urine, tears, saliva, bile, breast milk, mucus, semen, amniotic fluid, synovial fluid, cerebrospinal fluid, aqueous humor, pleural effusions, and any other secretion), and their levels reflect the delicate equilibrium between their release and clearance rates as well as the pathophysiological context. In this regard, circulating blood EVs have shown to be modulated by sex, 36 age, 37,38 exercise, 39 diet, 40 and other conditions as pregnancy 41 . Despite healthy states show presence of EVs, 42 their levels correlate with disease progression and severity, 43,44 even with the Framingham risk score 45,46 …”

NAMPT encapsulated by extracellular vesicles from young adipose-derived mesenchymal stem cells treated tendinopathy in a “One-Stone-Two-Birds” manner

“…A higher uptake rate could help ADMSC young -EVs produce a better protective effect. There were compressive differences in EV size, cargos and biological effects, which guided their application in the clinic, as summarized by a recent review [ 18 ]. In the analyses of NAD+ metabolism-related factors, key genes were dysregulated, except for NAMPT.…”

“…The expectation of a demographic shift to a higher elderly population structure in developed countries highlights the importance of senescence-related researches. Aging significantly influences the amount and biological function of EVs based on both clinical observations and experimental assays [ 18 ]. It has been reported that the beneficial effects of osteocyte-derived EVs diminished with aging [ 19 ], and similar outcomes were detected in MSCs [ 20 ].…”