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Blind mole rats (BMR) (Spalax, Nannospalax sp.) are extraordinary organisms with cancer resistance and a long lifespan for their size. Cellular senescence is a condition in which cells cease dividing irreversibly and secrete proinflammatory cytokines. To understand the mechanisms behind their superior traits, we utilized transcriptomics and proteomics tools in senescent BMR cells to compare them to similarly sized mice. The results revealed the alterations in Janus kinase (JAK) signaling and the cytokine-mediated pathway during the cellular senescence process in BMRs. These findings might reveal the novel mechanisms behind the unique biology of BMRs through cytokine-mediated adaptations.

The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK–STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK–STAT signaling were …