Investigation of the mechanisms that maintain homeostasis in the naked mole-rat, the longest-lived and cancer-resistant rodent

• Project/Area Number: 18H02365
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: Kumamoto University
• Principal Investigator: Miura Kyoko 熊本大学, 大学院先導機構, 准教授 (80583062)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2019: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000); Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: ハダカデバネズミ / naked mole rat

Outline of Final Research Achievements

The longest-lived rodent, the naked mole-rat (NMR), has strong resistance to aging and cancer. In general, chronic inflammation is closely related to aging-related diseases and carcinogenesis. In this study, we focused on the attenuation of inflammatory responses in NMR tissues. Chronic inflammation associated with obesity is one of the causes of metabolic diseases. We showed that the NMRs do not become obese by consuming a high-fat or high-sugar diet and does not show fatty liver or glucose intolerance. We found that reduced glucose metabolism in NMRs may be involved in this resistance. We also identified a novel gene mutation that may be involved in the NMR-specific attenuation of inflammatory responses.

Academic Significance and Societal Importance of the Research Achievements

これまで、慢性炎症と個体の老化・病態の進行の関わりについてモデル動物を用いて様々な研究が行われてきたが、顕著な老化関連疾患耐性を持つ動物種における当該経路の制御は未だ明らかとなっていない。デバ特異的な炎症抑制機構に着目した本課題では、炎症特性を規定すると考えられる代謝制御機構、炎症誘導制御機構の一端を解明する、非常に新規性の高い成果をあげた。これらの成果は、進化的に獲得された個体の恒常性維持に寄与する新たなメカニズムの理解や、将来的にヒトに老化耐性・がん化耐性をもたらす方法論の確立につながるものであり、非モデル動物を活用した老化・がん研究の進展に大きく貢献した。