| Project/Area Number |
18K08023
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | anti-aging / NM_026333 / coupling factor 6 / acidosis / channel / NCX1 / NCLX |
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| Outline of Final Research Achievements |
Based on the background that coupling factor 6 (CF6) accelerates acidosis-mediated aging though a causative gene NM_026333, we searched the target molecules and inhibitors of protein relevant to NM_026333. We found NCX1 (Na+-Ca2+ exchanger) as a target of NM_026333, and SN-6 is a selective inhibitor of NCX1. SN-6 rescued CF6-transgenic mouse-derived cells (TG cells) from multiple aging hallmarks, including epigenetic alteration, impaired autophagy, and nuclear membrane-related genomic instability, and elongated telomere length in the TG cells. We confirmed that telomere length of leukocytes was shorter in the TG mice at the age of 100 weeks compared with age-matched control mice, but was extended by 15% by intraperitoneal injection of CNAP (NM_026333 recombinant protein) or SN-6. Human gene that is relevant to mouse NM_026333 was undetected.
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| Academic Significance and Societal Importance of the Research Achievements |
老化抑制効果を有する新規NM_026333の結合蛋白がNCX1と同定され、その有用性が確認されたことは、創薬を考えた上で極めて重要である。これらの研究は、細胞内酸性化による老化促進機序にCF6がどのように関与するかを明らかにできた点で学術的な意義がある。NM_026333の結合蛋白はチャネル蛋白質であり、チャネルの阻害薬がCF6による細胞老化のみならず個体老化をも抑制した。CF6は老化を促進させ創薬に向けた分子標的となる可能性が大である。本研究の社会的意義は、老化の新しい機序の解明並びにCF6阻害剤の開発が開始され、健康寿命等の将来の医療に還元・貢献できることが期待されることである。
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