A novel prevention and treatment method of ocular aging by targeting sirtuins.
| Project/Area Number |
17H04353
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Keio University |
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Principal Investigator |
TSUBOTA Kazuo 慶應義塾大学, 医学部(信濃町), 教授 (40163878)
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| Co-Investigator(Kenkyū-buntansha) |
川島 素子 慶應義塾大学, 医学部(信濃町), 特任講師 (00327610)
稲垣 絵海 慶應義塾大学, 医学部(信濃町), 特任助教 (40464903)
栗原 俊英 慶應義塾大学, 医学部(信濃町), 特任准教授 (50365342)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | Sirtuin / CR / 酸化ストレス / ミトコンドリア / NAD関連代謝 / NMN / 抗加齢医学 / NAD代謝 / ドライアイ / 緑内障 / Fuchs角膜内皮変性症 / 眼科学 / NAD / 眼 |
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| Outline of Final Research Achievements |
In this study, we aimed to develop a new innovative prevention method for ocular diseases by targeting sirtuins. We established the measurement of nicotinamide adenine dinucleotide (NAD)-related metabolites which are known to activate sirtuins and measured the concentration of these NAD-related metabolites in the aqueous humor, plasma and cerebrospinal fluid. We investigated the anti-oxidative and anti-apoptotic effects of these NAD-related metabolites and obtained promising results in an anterior and posterior disease model both-in vitro and in vivo. Furthermore, we performed a clinical trial to confirm its safety in human by oral administration of Nicotinamide Mononucleotide (NMN) which can directly be converted to NAD. These results suggest that activation of sirtuins by administration of NAD-related metabolites could be a possible treatment for ocular aging diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本邦では高齢化社会を目前とし老化研究は重要課題である。中でも眼疾患は緑内障や白内障など年齢依存的に有病率が増加する疾患が多くを占める。本研究では長寿遺伝子Sirtuinを標的としその活性化に必要な分子であり、酸化還元の補酵素でもあるnicotinamide adenine dinucleotide(NAD)に着目して検討を行った。結果、NAD関連代謝産物の補完が眼疾患の予防の一助になりうる可能性を見出した。
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Report
(4 results)
Research Products
(66 results)
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[Journal Article] Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men2020
Author(s)
Irie J, Inagaki E, Fujita M, Nakaya H, Mitsuishi M, Yamaguchi S, Yamashita K, Shigaki S, Ono T, Yukioka H, Okano H, Nabeshima YI, Imai SI, Yasui M, Tsubota K, Itoh H
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Journal Title
Endocrine Journal
Volume: 67
Issue: 2
Pages: 153-160
DOI
NAID
ISSN
0918-8959, 1348-4540
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ketone body 3-hydroxybutyrate mimics calorie restriction via the Nrf2 activator, fumarate, in the retina.2018
Author(s)
Izuta Y, Imada T, Hisamura R, Oonishi E, Nakamura S, Inagaki E, Ito M, Soga T, Tsubota K.
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Journal Title
Aging Cell.
Volume: 17
Issue: 1
Pages: 1-15
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Light for Health.2019
Author(s)
Tsubota K.
Organizer
Picower Institute for Learning and Memory, Massachusetts Institute of Technology
Related Report
Int'l Joint Research / Invited
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[Presentation] 食品含有成分， NMN (nicotinamide mononucleotide)の高感度分析法の開発と霊長類モデルにおける体内動態の解明2019
Author(s)
稲垣絵海, 廣瀬枝実子, 菅井恵津子, 後藤恵子, 芝田晋介, 羽藤晋, 榛村重人, 佐藤泰憲, 中村紳一郎, 岡野栄之, 坪田一男.
Organizer
日本食品化学学会第25回総会・学術大会
Related Report
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[Presentation] Ketone body 3-hydroxybutyrateYusuke Izuta, Toshihiro Imada, Ryuji Hisamura, Shigeru Nakamura, Kazuo Tsubota. mimics calorie restriction via Nrf2 activator fumarate in retina2017
Author(s)
Izuta Y, Imada T, Hisamura R, Oonishi E, Nakamura S, Inagaki E, Ito M, Soga T, Tsubota K.
Organizer
Keystone Symposia: Aging and Mechanisms of Aging-Related Disease. Yokohama, Japan, 15-19 May 2017
Related Report
Int'l Joint Research
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