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Objectives Some organisms are long-lived and naturally resistant to cancer such as naked mole-rats (NMRs). Studies have shown that these animals can better tolerate stress due to mechanisms, such as upregulation of antioxidant pathways and improved proteostasis. In the present study, we aimed to analyze the tolerance against stress and the cellular mechanisms related to the stress response in NMR cells comparative to mouse cells. Materials and methods NMR and mouse fibroblasts were exposed to cellular stresses including H 2 O 2  and/or NaNO 3  and the viability of the cells were analyzed. In addition messanger RNA (mRNA) expression of antioxidant transcription factor Nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target gene NAD(P)H quinone dehydrogenase 1 (NQO1) were determined by qRT-PCR and comprehensive analysis of stress-related gene expression was performed by RNA-Sequencing in fibroblasts and induced pluripotent stem cells (iPSC). Results Surprisingly, NMR fibroblasts were found to be more sensitive than mouse cells to H 2 O 2  and NaNO 3 . Furthermore, it was shown that fibroblasts and iPSCs mainly aren’t identical in the expression pattern of cellular defense signaling and several factors are mainly downregulated in NMR iPSCs. Conclusions Collectively, the data gained from the present study help to improve the understanding of evolved mechanisms that contribute to stress resistance, aging and cancer.

Cellular stress responses of long-lived and cancer-resistant naked mole-rats