Mechanisms of Age-Related Disease Resistance in the Longest-Lived Rodent, the Naked Mole-Rat三浦 恭子1) Kawamura Y, Oka K, Semba T, et al. Cellular senescence induction leads to progressive cell death via the INK4a-RB pathway in naked mole-rats. EMBO J. 2023. 42(16):e111133.2) Oka K, Yamakawa M, Kawamura Y, et al. The naked mole-rat as a model for healthy aging. Annu Rev Anim Biosci. 2023. 11:207–226.熊本大学 大学院生命科学研究部 老化・健康長寿学講座／九州大学 大学院医学研究院 応用幹細胞医科学部門 長寿幹細胞医学分野7. 最長寿齧歯類ハダカデバネズミにおける加齢性疾患耐性メカニズムの探求The naked mole-rat (NMR) is the longest-lived rodent, with a lifespan exceeding 40 years. NMRs exhibit minimal age-related decline in physiological functions and remarkable resistance to age-related diseases such as cancer, Alzheimer’s, and cardiovascular disorders, making them a unique model for “healthy aging.” Our laboratory has optimized breeding techniques and currently maintains over 1,700 NMRs. We have identified several distinctive mechanisms underlying their disease resistance: a tumor-suppressive mechanism in NMR iPS cells; suppression of cancer-promoting inflammation through impaired necroptosis caused by RIPK3 and MLKL mutations; and a novel cell death-inducing pathway in senescent cells involving serotonin metabolism. These features contribute to reduced tissue inflammation and likely support the NMR’s exceptional longevity and resistance to age-related diseases. In this symposium, I will provide an overview of NMR biology and present our recent findings, which offer new insights into their unique aging resistance and potential implications for advancing human health and longevity. Department of Aging and Longevity Research, Faculty of Life Sciences, Kumamoto University / Laboratory of Longevity and Stem Cell Biology, Faculty of Medical Sciences, Kyushu UniversityKyoko Miura15
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