Expression of the p53 Network Aging-associated Genes shaken, not stirred in a 3-Week Microgravity Simulation Human Study

Background: The hostile space environment affects human health and aging. NASA has named five main hazards astronauts will face in space, including space radiation and changes in gravity. However, the contribution of each of these factors, along with others, to the overall impact on biomolecular and cellular processes is not always clear. Objective: To explore the effects of microgravity on the transcriptomes of healthy volunteers, with a focus on aging-related gene expression in p53 cell signaling pathways. Methods: Ten healthy young men were exposed to simulated microgravity (SMG) for three weeks and blood samples were collected at five time point before, during and after the course of SMG. T cells were purified from the peripheral blood samples and total RNA was isolated and sequenced followed by bioinformatics analysis of volunteers global transcriptomes. Results: A differential expression of p53 network genes was observed. The expression of nearly 30 genes involved in p53 gene network was affected during a 3-week course of simulated microgravity environment in dry immersion including classic p53 downstream target genes involved in cellular senescence: GADD45, p21, PUMA, IGF1 and other targets and potential target genes. Conclusion: For the first time, the p53-associated cell signaling pathways and gene network in human T cells were reported to be affected in vivo by dry immersion SMG. It is evident that the relatively mild effects of simulated weightlessness on the human body are sufficient to activate these pathways and influence aging-related genes in the p53 gene network. These findings should not be dismissed, as they could open the door to the discovery of a novel category of drugs - MG-senolytics.