Brain-muscle microphysiological system enabled extracellular vesicle network for understanding aging in space

ABSTRACT Unveiling the brain-muscle axis associated with aging could be a key to many diseases, including Alzheimer's disease (AD) and Parkinson’s disease (PD) prevention and rehabilitation. Several modes of communication between the brain and muscle have been explored in the research field, including the emerging route via circulating extracellular vesicles (EVs). Elucidating an EV-enabled communication network between the brain and skeletal muscle could reveal essential molecular targets and signaling pathways, resulting in more effective therapeutic strategies to prevent brain aging and expand health span. We hypothesize that vital molecular drivers indicating the effects of microgravity on human brain-muscle physiology could be revealed to correlate with age-associated conditions. In UG3 PHASE (Year 1-Year 2), we will focus on the on-ground development of brain-muscle MPS to be used in microgravity environments. We will Integrate with the flight hardware provided by implementation partner for payload, functioning in an automatic regime, and recapitulating key features of brain-muscle physiology to achieve initial flight testing. In UH3 PHASE (Year 3-Year 5), we seek to understand microgravity effects and regenerative EVs on human brain-muscle physiology to correlate with age-associated conditions for therapeutic development. We will integrate the second space flight testing to achieve anti-apoptotic and regenerative potency assessment for therapeutic development using regenerative EVs. Our long-term goal is to establish space enabling brain-muscle MPS to understand brain-muscle physiology in space and develop EVs as a practical therapy approach to prevent aging.