Extensive dynamic changes in the human transcriptome and its circadian organization during prolonged bed rest.

Area of Science:

• Chronobiology
• Molecular Biology
• Human Physiology

Background:

• The human transcriptome exhibits daily rhythms influenced by circadian clocks, behavior, and systemic factors.
• The impact of prolonged physiological challenges on the temporal organization of the human transcriptome remains largely unknown.
• Understanding these changes can provide insights into adaptation, disease, and recovery processes.

Purpose of the Study:

• To investigate the effects of a 90-day constant bed rest protocol on the temporal organization of the human transcriptome.
• To determine the extent and duration of transcriptome alterations under prolonged physiological stress.
• To identify molecular pathways affected by long-term challenges.

Main Methods:

• Analysis of 24-hour time-series transcriptome data from 20 individuals undergoing 90 days of constant bed rest.
• Application of dimensionality-reduction approaches to identify patterns in transcriptomic changes.
• Assessment of changes in the number, amplitude, and phase of rhythmic transcripts, including clock genes.

Main Results:

• A 90-day bed rest protocol significantly affected 91% of the human transcriptome.
• Transcriptomic alterations persisted, with 76% of affected transcripts still altered after 10 days of recovery.
• Affected transcripts were predominantly associated with mRNA translation and immune function pathways.
• Significant variations were observed in the rhythmicity (number, amplitude, phase) of transcripts, including core clock genes.

Conclusions:

• Prolonged physiological challenges induce profound and lasting changes in the temporal organization of the human transcriptome.
• These findings highlight the transcriptome's sensitivity to sustained stressors and its slow recovery.
• The results have implications for understanding the health consequences of conditions like microgravity and prolonged bed rest, informing potential countermeasures.