Extracellular vesicles represent a promising platform for understanding systemic adaptation and disease progression. Our research investigates how extracellular vesicle cargo reflects physiological changes associated with spaceflight, aging, disuse, and Duchenne muscular dystrophy (DMD). By integrating biomarker discovery, multi-omics profiling, and translational biology, we aim to develop extracellular vesicle–based approaches for monitoring musculoskeletal health, understanding disease mechanisms, and advancing precision therapeutics for human health on Earth and in space.