Proceedings of the National Academy of Sciences
Naked mole rats can undergo developmental, oncogene-induced and deoxyribonucleic acid damage-induced cellular senescence.

The naked mole rat is the longest-lived rodent with a maximum life span of over 30 years. Furthermore, naked mole rats are resistant to a variety of age-related diseases and remain fit and active until very advanced ages. The process of cellular senescence has evolved as an anticancer mechanism. However, it also contributes to aging and age-related pathologies. Here, we characterize cellular senescence in the naked mole rat. We find that naked mole rat cells undergo three major types of cellular senescence - developmental, oncogene-induced, and deoxyribonucleic acid damage-induced. Senescent naked mole rat cells displayed many common features with senescent mouse cells, including activation of a senescence-associated secretory phenotype. These results demonstrate that the naked mole rat retains the major types of cellular senescence responses despite its exceptional longevity.

Cellular senescence is an important anticancer mechanism that restricts proliferation of damaged or premalignant cells. Cellular senescence also plays an important role in tissue remodeling during development. However, there is a trade-off associated with cellular senescence as senescent cells contribute to aging pathologies. The naked mole rat - Heterocephalus glaber - is the longest-lived rodent that is resistant to a variety of age-related diseases. Remarkably, naked mole rats do not show aging phenotypes until very late stages of their lives. Here, we tested whether naked mole rat cells undergo cellular senescence. We report that the naked mole rat displays developmentally programmed cellular senescence in multiple tissues, including nail bed, skin dermis, hair follicle, and nasopharyngeal cavity. naked mole rat cells also underwent cellular senescence when transfected with oncogenic Ras. In addition, cellular senescence was detected in naked mole rat embryonic and skin fibroblasts subjected to γ-irradiation. However, naked mole rat cells required a higher dose of γ-irradiation for induction of cellular senescence, and naked mole rat fibroblasts were resistant to γ-irradiation induced apoptosis. Gene expression analyses of senescence-related changes demonstrated that, similar to mice, naked mole rat cells up-regulated senescence-associated secretory phenotype genes but displayed more profound down-regulation of deoxyribonucleic acid metabolism, transcription, and translation than mouse cells. We conclude that the naked mole rat displays the same types of cellular senescence found in a short-lived rodent.