Gene-metabolite network linked to inhibited bioenergetics in association with spaceflight induced loss of quadriceps muscle

Prolonged residence of mice in spaceflight is a scientifically robust and ethically ratified model of muscle atrophy caused by continued unloading. Under the Rodent Research Program of NASA, we assayed the genomic and metabolomics perturbations in the quadriceps of C57BL/6J male mice that lived on the spaceflight (FLT) or at Ground Control (CTR) for approximately four weeks. Wet weight of quadriceps were significantly reduced in FLT mice. Deep next generation sequencing and untargeted mass spectroscopic assay interrogated the gene-metabolite landscape of same tissues. A majority of top ranked differentially suppressed genes in FLT encode proteins from myosin or troponin family suggesting a sarcomere alteration in space. Significantly enriched gene-metabolite networks were found linked to saromeric integrity, immune fitness and oxidative stress response; all inhibited in space as per in silico prediction. A significant loss of FLT mitochondrial DNA copy numbers underlined the energy deprivation associated with spaceflight induced stress, and this hypothesis was reinforced by the omics analysis that showed inhibited networks related to protein, lipid and carbohydrate metabolism, and ATP synthesis and hydrolysis. Finally, we reported a list of upstream regulators, which could be targeted for next generation therapeutic intervention for the betterment of the musculoskeletal system in male mice subjected to chronic disuse. Abbreviation Key: Sham surgical procedure done (Sh); non-surgical control (NS); Ground Control group (G); Flight Group (F); Whole Body frozen as sample on ISS (W).

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  "026:00"
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  "026:000"
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[
  "Biological and Physical Sciences"
]