Spaceflight Is Associated with an Age-Conserved Kidney Transcriptomic Signature Linked to Inflammation, Tubular Channelopathy, and Senescence

Spaceflight (FLT) exposes astronauts to physiological stressors that may impact kidney function, but the molecular mechanisms and their relevance to established kidney disease pathways across biological ages remain incompletely defined. We profiled kidney transcriptomes from NASA GeneLab dataset OSD-771/GLDS-674 (Rodent Research Reference Mission-2), comprising bulk mRNA sequencing of kidney tissue from female C57BL/6NTac mice flown for 55–58 days aboard the International Space Station (FLT) versus matched ground controls (BSL), evaluated independently in young (12-week) and mature (29-week) cohorts. Differentially expressed genes (DEGs) were identified for each age group and additionally ranked by a composite pi-score [log2(fold change) × −log(p)]. Genes meeting both DEG significance and top-50 pi-score criteria in both age groups were defined as the age-conserved FLT kidney signature. FLT was associated with a 7-gene kidney signature comprising 6 upregulated transcripts, d630029k05rik, gm11992, hao2, igfbp1, aplnr, naaladl1, and 1 downregulated transcript, cry1, with tight pairwise co-expression (|r| = 0.80–0.96). Gene Ontology Biological Process (GO BP) overrepresentation analysis linked this age-conserved signature to three pathological axes, viz. inflammation, tubular channelopathy, and cellular senescence. These data inform kidney risks during FLT.