Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Aging (Albany NY). 2021 Jan 28;13(3):3239-3253. doi: 10.18632/aging.202577.
The naked mole rat (NMR), is the longest-living rodent species, and is extraordinarily resistant to cancer and aging-related diseases. The molecular basis for these unique phenotypic traits of the NMR is under extensive research. However, the role of regulated cell death (RCD) in the longevity and the protection from cancer in the NMR is still largely unknown. RCD is a mechanism restricting the proliferation of damaged or premalignant cells, which counteracts aging and oncotransformation. In this study, DNA damage-induced cell death in NMR fibroblasts was investigated in comparison to RCD in fibroblasts from . The effects of methyl methanesulfonate, 5-fluorouracil, and etoposide in both cell types were examined using contemporary cell death analyses. Skin fibroblasts from were found to be more resistant to the action of DNA damaging agents compared to fibroblasts from . Strikingly, our results revealed that NMR cells also exhibit a limited apoptotic response and seem to undergo regulated necrosis. Taken together, this study provides new insights into the mechanisms of cell death in NMR expanding our understanding of longevity, and it paves the way towards the development of innovative therapeutic approaches.
裸鼹鼠（NMR）是寿命最长的啮齿动物物种，对癌症和与衰老相关的疾病具有非凡的抵抗力。NMR 这些独特表型特征的分子基础正在广泛研究中。然而，调控细胞死亡（RCD）在 NMR 的长寿和预防癌症中的作用在很大程度上仍然未知。RCD 是一种限制受损或癌前细胞增殖的机制，可对抗衰老和癌变。在这项研究中，与 中的 RCD 相比，研究了 NMR 成纤维细胞中 DNA 损伤诱导的细胞死亡。使用现代细胞死亡分析研究了甲基甲磺酸酯、5-氟尿嘧啶和依托泊苷对两种细胞类型的作用。与 中的成纤维细胞相比，发现来自 的皮肤成纤维细胞对 DNA 损伤剂的作用具有更强的抗性。引人注目的是，我们的结果表明 NMR 细胞也表现出有限的凋亡反应，似乎经历了调控性坏死。总之，这项研究为 NMR 中的细胞死亡机制提供了新的见解，扩展了我们对长寿的理解，并为开发创新的治疗方法铺平了道路。
