Senescent cell-derived extracellular vesicles as potential mediators of innate immunosenescence and inflammaging

Ageing is accompanied by a decline in immune function (immunosenescence), increased inflammation (inflammaging), and more senescent cells which together contribute to age-related disease and infection susceptibility. The innate immune system is the front-line defence against infection and cancer and is also involved in the removal of senescent cells, so preventing innate immunosenescence and inflammaging is vital for health in older age. Extracellular vesicles (EVs) modulate many aspects of innate immune function, including chemotaxis, anti-microbial responses, and immune regulation. Senescent cell derived EVs (SEVs) have different cargo to that of non-senescent cell derived EVs, suggesting alterations in EV cargo across the lifespan may influence innate immune function, possibly contributing to immunosenescence and inflammaging. Here we review current understanding of the potential impact of miRNAs, lipids and proteins, found in higher concentrations in SEVs, on innate immune functions and inflammation to consider whether SEVs are potential influencers of innate immunosenescence and inflammaging. Furthermore, senolytics have demonstrated an ability to return plasma EV content closer to that of non-senescent EVs, therefore the potential use of senotherapeutics (senolytics and senostatics) to ameliorate the effects of SEVs on immunosenescence and inflammaging is also considered as a possible strategy for extending health-span in older adults.