Human Leukocyte Transcriptome Changes During The Transition To And From 60 Days Of Bed Rest

PURPOSE: We sought to investigate the effect of unloading and physical inactivity typical of the bed rest model by identifying leukocyte transcriptome changes in participants that underwent 60 days of bed rest followed by reambulation. Previous work from our lab utilized a time course analysis and identified temporal expression changes in 2,415 protein-coding transcripts (Stratis et al., 2022). Our current work is focused on selective time-point comparisons to reveal expression changes in both coding and non-coding genes specific to the bed rest and reambulation study phases. METHODS: This longitudinal study design collected ten blood samples from twenty healthy male participants. We measured gene expression through RNA sequencing of leukocytes and applied linear mixed modelling to assess differential expression at the following time-points: model 1, baseline data collection (BDC) (BDC-12 and BDC-11 combined) vs head-down tilt (HDT) bed rest (HDT1, HDT2, HDT30, HDT60); and model 2, HDT60 vs reambulation (R1, R2, R12, R30). RESULTS: Model 1 found 30/44 (68%) differentially expressed genes (α < 0.05 & log fold change>|1|) were between baseline and early bed rest (BDC-12/-11 vs HDT2). Model 2 found 24/37 (65%) differentially expressed genes were between late bed rest and early reambulation (HDT60 vs R1). CONCLUSIONS: Major transcriptome changes occurred early at the transitions to and from bed rest. Current findings can guide future work on the complex responses and adaptation mechanisms experienced during physical inactivity and unloaded environments.