Time-averaged simulated microgravity ameliorates tau-induced deficit in Drosophila melanogaster

Space exploration presents environmental challenges, including microgravity, high-energy radiation, and extreme temperature changes. Accelerated aging in space provides a unique opportunity to study age-related neurodegenerative diseases. Tauopathies, such as Alzheimer's disease, are characterized by neurofibrillary tangles of hyperphosphorylated tau protein in the brain. We studied how time-averaged simulated microgravity (taSMG), which replicates space conditions, affects tauR406W-induced neurotoxicity in transgenic flies. Applying taSMG at an early stage of neurodegeneration reduced severe locomotion impairment in tauR406W-expressing flies. This protective effect was sustained, specific to the tau mutation, and dependent on the timing, duration, and severity of tau expression. Transcriptomic analysis revealed that taSMG normalizes gene expression related to the extracellular environment, innate immune response, and olfactory function. These results underscore gravity's role in modulating tauopathy and suggest that microgravity may potentially offer new therapeutic insights for neurodegenerative diseases.