Accepted_test

The naked mole rat , Heterocephalus glaber, is the longest living rodent species and is extremely resistant to cancer and diseases associated with aging. This animal is distinguished by a record-breaking maximum life expectancy for rodents, increased resistance to cancer, and a number of other unique phenotypic traits; its genome and proteome are characterized by stability and efficient functioning. All this gave reason to assume that the molecular “machines” that resist the accumulation of damage in the H. glaber genome, including DNA repair mechanisms, function with high efficiency. Mechanisms of regulated cell death may be directly related to resistance to induced cancer tumors. However, the question of how effectively and which mechanisms regulate cell death and respond to genotoxic insults in H. glaber cells remains unresolved. Using the approaches we developed, we experimentally tested these assumptions by comparing the efficiency of the H. glaber and mouse nucleotide base excision repair systems. Taken together, our results provide evidence that H. glaber has more efficient excision repair systems , which may contribute to the longevity and cancer resistance of this species. As part of our investigation of the molecular basis of the unique phenotypic features, we also examined the effects of cellular exposure of H. glaber and mouse fibroblasts to methyl methanesulfonate, 5-fluorouracil, and etoposide. Using modern analytical methods, we found that Heterocephalus glaber skin fibroblasts are more resistant to DNA damaging. Our results showed that NMR cells exhibit a limited apoptotic response and can also undergo regulated necrosis.