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

The University of Florida received a $2,344,810 cooperative agreement from the National Center for Advancing Translational Sciences (NCATS, CFDA 93.350) awarded on August 1, 2025, through July 31, 2027. The award supports development of a brain-muscle microphysiological system (MPS) enabled by extracellular vesicles (EVs) to understand aging mechanisms in microgravity environments. The research addresses the brain-muscle axis as a potential key to preventing neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. The project will occur in two phases: a UG3 phase (Years 1-2) focused on ground-based development and initial flight testing of the brain-muscle MPS integrated with flight hardware, and a UH3 phase (Years 3-5) dedicated to understanding microgravity effects on brain-muscle physiology and assessing regenerative potential of EVs for therapeutic development through second-phase space flight testing.

Two sub-awardees support critical project components. Brigham & Women's Physician Organization received a subaward effective January 22, 2026, providing scientific oversight of the Brain4Muscle Microphysiological Analysis System (BM4MAP) design. The University of Colorado, through its BioServe facility, received a subaward effective October 30, 2025, to provide comprehensive mission integration and engineering support services for space flight certification of the tissue chip microfluidic system, including flight project management, science definition support, design reviews, and integration testing with NASA-approved hardware for International Space Station deployment.

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.