Circadian regulation of extracellular vesicle biogenesis, composition, and release

Circadian rhythms in mammals are governed by cell-autonomous oscillators that synchronize physiological functions through central and peripheral communication. Extracellular vesicles (EVs) mediate intercellular and systemic signaling, with time-of-day-dependent release and cargo composition regulated by the circadian clock. This regulation involves both transcriptional and post-transcriptional mechanisms affecting genes involved in EV biogenesis. Studies in diverse models show EVs impact physiological and pathological processes, including inflammation, cardiovascular disease, chronic kidney disease, and cancer. EVs also serve as important biomarkers, especially in cancer. The accompanying article explores how clock proteins regulate multiple aspects of EV biology and highlights the significance of circadian dysregulation in EV-associated pathologies. Understanding EV-mediated signaling within the framework of circadian rhythms is critical for improving disease diagnosis, informing treatment strategies, developing therapeutic applications, and enhancing the diagnostic utility of EVs. This insight may pave the way for novel chronotherapy approaches in clinical practice.