The proposal aims to validate circulating small noncoding RNAs (sncRNAs) as early biomarkers for microgravity- and cosmic radiation-induced physiopathological alterations in astronauts. This includes damages to multiple organs, immune system modulation, and infections. Unlike other biomarkers, sncRNAs are numerous, cell/state specific, and resistant to degradation, making them ideal for precision biomarker analyses. Besides microRNAs (miRNAs), altered expression of tRNA fragments (tRF) and Piwi-interacting RNA (piRNA) in various pathological conditions has been reported. The proponents, experienced in sncRNA biology, have identified cell/tissue-specific sncRNAs and quantified them in various body fluids. The plan involves identifying relevant sncRNA alterations induced by microgravity using pre-existing Genelab datasets, using Machine Learning (ML) simulations to model sncRNA changes as potential stress/disease indicators over time in space and after landing. New samples from body fluids and specimens will validate the model, identifying dysregulated sncRNA signatures, their targets, and biological processes altered by spaceflight. Impact on future missions includes validating sncRNAs as measurable biomarkers for astronauts' physiological reactions to microgravity, potentially enabling self-analyses and prompt actions before conditions become pathological. The study's impact on terrestrial life involves considering astronauts as models of accelerated aging, with identified sncRNA signatures potentially transferring to diagnosing or prognosing patients and developing point-of-care apparatus for clinicians and healthcare professionals.