Microgravity Impacts the Expression of Aging-Associated Candidate Gene Targets in the p53 Regulatory Network

The extreme space environment accelerates aging and compromises human health. NASA has named five main hazards in space, including gravity changes. However, the contribution of each factor to the overall impact on biomolecular and cellular processes is not always clear. We aimed to explore the effects of microgravity on the transcriptomes of healthy volunteers, with a focus on gene expression in p53 pathways. Ten healthy men were exposed to dry immersion simulated microgravity (DI-SMG) for three weeks and blood samples were collected at five timepoints before, during and after the course of DI-SMG. T cells were purified from the peripheral blood samples and total RNA was isolated and sequenced followed by a bioinformatics analysis of the volunteers' global transcriptomes. A differential expression of p53 network genes was observed. The expression of 30 genes involved in the p53 gene network was affected during a 3-week course of DI-SMG including classic p53 downstream target genes involved in cellular senescence: GADD45, p21, PUMA, IGF1 and other target genes. For the first time, the p53-associated cell signaling pathways and gene networks in human T cells were reported to be affected in vivo by DI-SMG. It is evident that the relatively mild effects of simulated weightlessness on the human body are sufficient to activate these pathways. Identified transcriptomic changes point toward a potential molecular overlap with aging and cellular senescence. These findings could contribute to a broader research landscape that may lead to the discovery of a new class of drugs-MG-senolytics.