Food Derived Bioactive Compounds in Mirna Mediated Bone and Muscular Regeneration and Remodelling under Microgravity: Use of Big Data and Bioinformatic Platforms

Altered gravity is known to modulate cellular gene expression, leading to physiological adaptations accompanied by changes in circulating biomarkers, including microRNAs (miRNAs). During long-duration space missions, exposure to microgravity contributes to musculoskeletal degeneration, including muscle atrophy and bone loss, which represent major health risks for astronauts. MiRNAs play key regulatory roles in gene expression and biological pathways associated with diseases and microgravity- induced conditions. It is well known that food-derived bioactive compounds (BCs) can directly or indirectly influence miRNA expression and related genes, thereby affecting cellular pathways involved in bone and muscle regeneration.In this study, we employed an integrated bioinformatics approach to investigate the molecular mechanism underlying microgravity-associated musculoskeletal alterations. Specifically, we identified differentially expressed miRNAs shared among osteoporosis, muscle atrophy, and simulated microgravity conditions. Using MIENTURNET and Reactome tools, we characterised their target genes and pathways and explored food-derived BCs capable of modulating these miRNAs, genes, and pathways.Our analysis identified a set of 13 miRNAs shared among the three conditions (miR-21, miR-24–3p, miR-23b, miR-29a-3p, miR-23a, miR-155–5p, miR-223, miR-98, miR-25, let-7g-5p, miR-27a, miR-148a, miR-206) which revealed significant overlaps in genes and pathways, suggesting conserved molecular mechanisms linking bone and muscle degeneration to microgravity-induced changes.Notably, we identified interactions between BCs and key miRNAs including ursolic acid with let-7g-5p and quercetin with miR-206. Tocotrienol and epicatechin were associated with upregulation of miR-206, potentially supporting myoblast differentiation and muscle regeneration. Additional compounds identified through the STITCH database, such as curcumin, carotene, quercetin, and myricetin, target genes implicated in metabolic regulation and tissue remodelling (ccnd1, scarb1, pim1), indicating a broad modulatory potential.Overall, these results provide novel insights into the molecular mechanisms underlying microgravity-induced musculoskeletal and metabolic alterations. They also highlight food-derived BCs as promising nutritional countermeasures to mitigate health risks during long-duration space missions. These results have translational relevance for terrestrial disease-related conditions and are also potentially correlated with pathological condition such as osteoporosis and muscle atrophy, which are also associated with ageing.