Functional significance of extracellular vesicles as mediators of cardiometabolic and cardiorenal diseases upon aging.

Aging increases the risk of cardiometabolic and cardiorenal disease and this is associated with cellular dysregulation including oxidative stress, chronic inflammation, insulin resistance and senescence(definition). Extracellular vesicles (EV) facilitate inter-organ communication and are now well established as important pathophysiological mediators in many aging-associated diseases. Our knowledge of EV biosynthesis, cargo composition, cellular targeting and functional effects has expanded significantly over the past decade. Here we provide a comprehensive review on the characteristics and functional significance of EV in cardiometabolic and cardiorenal diseases in the context of aging. Specifically, we focus on heart failure, type 2 diabetes, metabolic dysfunction-associated steatohepatitis (MASH), hypertension, and chronic kidney disease and discuss aging-associated changes in bioactive molecules transferred via EV and how these are associated with healthspan(definition). Furthermore, we summarize current potential therapeutic applications of EV. Overall, this review summarizes current knowledge indicating an important role for EV in aging-related cardiometabolic and cardiorenal diseases, and how insights from basic research can potentially be translated to the clinic in order to combat aging-associated metabolic decline and improve longevity and healthspan.