Cellular Senescence in the Absence of Galactic Cosmic-Ray Muons

Cellular senescence is a stress response that prevents the proliferation of damaged cells. As senescence has evolved in the near-surface biosphere, where cosmic background radiation (CBR) continuously delivers a low flux of highly penetrating muon particles, we investigated whether this persistent abiotic stress contributes to senescence thresholding. At the Canfranc Deep Underground Laboratory, an astrophysical facility located 800 meters beneath granite rock in the Spanish Pyrenees (~2,450 meters of water-equivalent depth), cosmic muons are suppressed by five orders of magnitude. There, we examined the senescence-induction dynamics in human cancer cells exposed to G0/G1- or G2/M-targeting chemotherapeutics and compared them to cells in adjacent, above-ground conditions with natural CBR. Muon depletion significantly reduced the acquisition of the senescence-associated β-gal-positive phenotype under conditions favoring a G0/G1 arrest with the CDK4/6 inhibitor palbociclib. SA-β-gal-positive states driven by G2/M arrest in response to the mitotic kinase inhibitor alisertib and the DNA-damaging radiomimetic bleomycin were insensitive to muon suppression. While the SENCAN classifier, which uses RNA-seq data to determine whether cell samples are senescent, and the senescence-associated secretory phenotype profiles were largely unaffected by the absence of cosmic-ray muons, muon depletion caused small variations at a transcriptome-wide level in the two pathways to senescence. Our hypothesis-generating study suggests that muons might act as abiotic signal-to-noise calibrators that facilitate the consolidation of senescence trajectories specifically associated with G0/G1 withdrawal. Our exploratory findings shed light on how life incorporated CBR evolutionarily to sense and respond to cellular damage, which could inform senescence operability in low-muon extraterrestrial habitats.