Space radiation induces distinct senescent phenotypes: Implications for space travel [bulk RNA-Seq]

Space radiation, comprising high-energy and high-charge ions, creates distinct clusters of DNA damage and dense macromolecular damage that result in the accumulation of senescent cells (SnCs) known to play a critical role in promoting multimorbidity. Here, we demonstrate that human fibroblasts exposed to different forms of space radiation acquire senescence-associated phenotypes including morphological alterations and the accumulation of SA-beta-gal+ cells to a greater extent than what is observed following gamma-irradiation.

Bulk and single cell RNA (scRNAseq) sequencing analysis revealed that space irradiated human fibroblasts up-regulated senescent-like phenotypes to a greater extent compared to gamma-irradiation and enriched pathways associated with chronic activation and adaptation of the integrated stress response and NADPH-coupled redox metabolism. Healthy cells treated with conditioned media from irradiated SnCs manifested pro-inflammatory transcriptional profiles dependent on both radiation and cell type.