Cologne Seminars on Ageing "Cell Death and Senescence Regulation in the Longest-Lived Rodent, the Naked Mole-Rat"

About Miura´s talk:

The naked mole-rat (NMR) is the longest-lived rodent with remarkable resistance to aging and cancer. We have previously demonstrated several mechanisms that likely contribute to the NMR's resistance to carcinogenesis and delayed aging. NMR iPS cells exhibit tumor-resistance due to species-specific activation of the tumor suppressor ARF and a loss-of-function mutation in the oncogene ERAS (Miyawaki et al., Nat. Commun. 2016). NMR neural stem cells (NSCs) are more resistant to gamma-irradiation than mouse NSCs (Yamamura et al., Inflamm. Regen. 2021). Upon induction of cellular senescence, NMR fibroblasts progressively undergo cell death through activation of the INK4a-RB pathway and serotonin metabolism, which may function as "natural senolysis" to inhibit the accumulation of senescent cells (Kawamura et al., EMBO J. 2023). We have also discovered that NMR tissues exhibit remarkable resistance to chemical carcinogenesis induction through a dampened inflammatory response. As a mechanism, we have identified an inability to induce necroptosis, a type of inflammatory programmed cell death, due to loss-of-function mutations in RIPK3 and MLKL (Oka et al., Commun. Biol., 2022). Recently, we have started to breed Damaraland mole-rats, a relative of the NMR, for comparative studies. In this seminar, I will discuss our previous research and recent progress.