Assessing Effects of Microgravity on Cardiovascular Aging with AI and 3D Organoids - Project Summary Astronauts often experience health challenges after spaceflight due to the body's adaptations to a microgravity environment. This UG3/UH3 project aims to explore how spaceflight impacts heart health, specifically focusing on the changes that occur in human heart under microgravity. Using stem cells, we will create 3D heart-like tissues, known as vascularized cardiac organoids (vCOs), which contain both heart cells and blood vessel cells. These organoids will be sent to the International Space Station (ISS) to study the effects of spaceflight on their function over time, including changes in their ability to beat, metabolize energy, and respond to inflammation. Our primary goals are to identify the biological pathways disrupted by spaceflight and to evaluate potential drugs that could protect the heart from these effects. We will use single-cell RNA sequencing, which allows us to observe how individual cells respond to spaceflight, combined with computational drug screening to identify promising therapeutic candidates. By comparing the responses of organoids in space with those grown on Earth, we aim to gain insights into how microgravity and space radiation affect heart function and identify new strategies for maintaining heart health during extended space missions. The findings from this study will improve astronaut safety during long-duration missions, such as those to Mars, by identifying effective countermeasures against space-induced cardiovascular changes. Additionally, the research could have broader implications for understanding heart health on Earth, potentially benefiting individuals with heart disease or inflammatory conditions. Our work seeks to bridge the gap between space-based and Earth-based heart research, offering new perspectives that could lead to innovative therapies for sustaining cardiovascular health in challenging environments.