Haematopoietic stem cells (HSCs) maintain balanced blood cell production in a process
called haematopoiesis. As humans age, their HSCs acquire mutations that allow some HSCs to
disproportionately contribute to normal blood production. This process, known as age-related
clonal haematopoiesis, predisposes certain individuals to cancer, cardiovascular and pulmonary
pathologies. There is a growing body of evidence suggesting that factors outside cells, such as
extracellular vesicles (EVs), contribute to the disruption of stem cell homeostasis during aging.
We have characterized blood EVs from humans and determined that they are remarkably
consistent with respect to size, concentration and total protein content, across healthy subjects
aged 20-85 yr. When analyzing EV protein composition from mass spectroscopy data, our
machine-learning-based algorithms are able to distinguish EV proteins based on age, and suggest
that different cell types dominantly produce EVs released into the blood, which change over time.
Importantly, our data shows blood EVs from middle and older age groups (>40 yr) significantly
stimulate haematopoietic stem cells (HSCs) in contrast to untreated and EVs sourced from young
subjects. Our study establishes for the first time that although EV particle size, concentration and
total protein content remain relatively consistent over an adult lifespan in humans, EV content
evolves during aging and potentially influences HSC regulation.
- Extracellular vesicles
- Stem Cells
- Clonal Haematopolesis