Identification of Therapeutics to Improve Astronaut Health in Space

During extended space missions, astronauts experience physiological shifts akin to accelerated aging. Microgravity induces muscle atrophy and bone density reduction, mirroring aging-related osteoporosis and muscle weakness. Cardiovascular deconditioning in space parallels aging effects on the heart, such as diminished blood pressure regulation and heart function. Additionally, exposure to space radiation heightens cancer risks and central nervous system damage, reflecting the damage seen in aging. Many of these terrestrial changes have been shown to be modulated using therapeutics that target the underlying mechanisms of aging. Ora Biomedical, Inc is a leader in the field of longevity intervention discovery and is uniquely poised to identify novel therapeutics that may protect against the adverse physiological outcomes of spaceflight. Using the invertebrate C. elegans and the WormBot-AI platform, Ora Biomedical has developed a high throughput drug discovery pipeline. This proposal will alter that pipeline to recapitulate and subsequently treat the adverse effects of spaceflight within terrestrial invertebrates. Phase I will consist of screening known FDA approved positive modulators of longevity and health span within invertebrates that have been subjected to conditions that mimic the stressors of spaceflight. Phase II would include a study of C. elegans expanded across more strenuous conditions than Phase I and across all FDA-approved compounds. Long term success in Phase II would lead to a limited clinical trial for participating astronauts. C. elegans has become a pivotal model in biomedical research due to its short lifespan, genetic manipulability, and well-understood biology. This nematode's use extends into aerospace research, where it was used to study the impact of microgravity and cosmic radiation on biological processes. Studies using C. elegans aboard space missions have explored alterations in gene expression related to muscle and neuronal function, mimicking aging on Earth. These investigations offer insights into the mechanisms driving aging and identify potential interventions to mitigate age-related decline, underscoring the worm's significant contribution to gerontology and space biology. Aim 1 of this research seeks to develop an Earth-based C. elegans model to replicate space conditions, utilizing prior nematode spaceflight studies as a baseline. Ora Biomedical will simulate space-like radiation in vivo, assessing nematode lifespan and health span via the WormBot-AI pipeline. Aim 2 involves screening 100 FDA-approved drugs, enriched for ones suspected or shown to target aging pathways, to determine their capability in offsetting the detrimental health impacts seen in space-mimetic conditions. Leveraging the known safety profiles of these drugs, this phase aims to accelerate their adoption for space travel, conducting thorough phenotypic analyses on C. elegans to pinpoint potential therapies relevant for space-travel.