Space radiation induces distinct senescent phenotypes: Implications for space travel

Area of Science:

• Astrobiology
• Cellular Biology
• Radiation Biology

Background:

• Earth's magnetic field is weakening, increasing exposure to space radiation.
• Space radiation, composed of high-energy ions, causes significant DNA and cellular damage.
• Accumulation of senescent cells (SnCs) is linked to multimorbidity and aging.

Purpose of the Study:

• To investigate the differential effects of space radiation versus gamma irradiation on human fibroblasts.
• To analyze the molecular mechanisms underlying radiation-induced cellular senescence.
• To evaluate the efficacy of senotherapeutics against space radiation-induced senescence.

Main Methods:

• Exposure of human fibroblasts to various forms of space radiation and gamma irradiation.
• Assessment of senescence-associated phenotypes (morphological changes, SA-β-gal staining).
• Bulk and single-cell RNA sequencing (scRNAseq) for transcriptional profiling.
• Treatment of cells with conditioned media from irradiated SnCs and senotherapeutics.

Main Results:

• Space radiation induced greater senescence-associated phenotypes in human fibroblasts compared to gamma irradiation.
• scRNAseq revealed upregulation of integrated stress response and redox metabolism pathways in space-irradiated cells.
• Conditioned media from irradiated SnCs induced pro-inflammatory profiles in healthy cells, dependent on radiation type and cell type.
• Senotherapeutics exhibited radiation-specific effects in primary dermal fibroblasts.

Conclusions:

• Space radiation differentially induces cellular senescence compared to gamma irradiation.
• Radiation-induced senescence may contribute to the pathogenic effects of space travel.
• Understanding these effects is crucial for mitigating health risks associated with space exploration and on Earth.