Spaceflight Activates Autophagy Programs and the Proteasome in Mouse Liver

Area of Science:

• Space biology
• Metabolomics
• Transcriptomics

Background:

• Spaceflight causes oxidative stress, potentially impairing cellular defense mechanisms.
• Previous studies indicated reduced glutathione levels in mice after space exposure, suggesting compromised oxidative defense.

Purpose of the Study:

• To investigate the multi-omic (metabolomic and transcriptomic) changes in mice exposed to spaceflight.
• To understand the molecular mechanisms underlying oxidative stress and cellular responses during space missions.

Main Methods:

• Unbiased, unsupervised, and integrated multi-omic analyses of metabolomic and transcriptomic data.
• Mice were exposed to spaceflight aboard the Space Shuttle Atlantis for 13.5 days.
• Enrichment analyses were performed on metabolite and gene sets.

Main Results:

• Significant alterations in osmolyte concentrations and glycerophospholipid/sphingolipid metabolism, potentially due to dehydration.
• Increased enrichment of aminoacyl-tRNA biosynthesis and purine metabolic pathways.
• Upregulation of genes associated with autophagy and the ubiquitin-proteasome system, alongside downregulation of Nrf2-mediated signaling.

Conclusions:

• Spaceflight induces metabolic shifts and activates cellular degradation and senescence pathways.
• Decreased hepatic oxidative defense may contribute to aberrant tRNA processing and mitochondrial dysfunction.
• These findings highlight molecular adaptations and potential health risks associated with the spaceflight environment.