Analysis of circadian misalignment using Mouse Cohort Model
| Project/Area Number |
19K22516
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 48:Biomedical structure and function and related fields
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Yagita Kazuhiro 京都府立医科大学, 医学(系)研究科(研究院), 教授 (90324920)
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| Project Period (FY) |
2019-06-28 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 概日リズム / 生体リズム / 体内時計 / 時計遺伝子 / シフトワーク / 未病制御 / 慢性炎症 / 免疫老化 / 概日リズム障害 / マウスコホート / 環境因子 / リバーストランスレーショナル研究 |
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| Outline of Research at the Start |
２４時間社会がもたらす生活時間と体内時計の「ズレ」は、様々な疾患リスクと相関があることがヒト疫学研究で示されている。しかし、現代社会の喫緊の健康課題であるにもかかわらず、因果性を検証した科学的エビデンスが極めて乏しく、未だに有効な予防法や対策を講じることができていない。本研究では、現実の課題解決に向けたリバーストランスレーショナル研究として、「マウスコホート」モデル系を用いて「環境と生体の時間的不適合」が引き起こす病態メカニズム解明を目指す。
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| Outline of Final Research Achievements |
Modern society characterized by a 24/7 lifestyle leads to misalignment between environmental cycles and endogenous circadian rhythms. Persisting circadian misalignment leads to deleterious effects on health and healthspan. However, the underlying mechanism remains not fully understood. Here, we subjected adult, wild-type mice to distinct chronic jet-lag paradigms named “mouse cohort model”, which showed that long-term circadian misalignment induced significant early mortality. We observed enhanced steatohepatitis with infiltration of inflammatory cells. The investigation of senescence-associated immune cell subsets from the spleens and mesenteric lymph nodes revealed an increase in PD-1+CD44high CD4 T cells as well as CD95+GL7+ germinal center B cells, indicating that the long-term circadian misalignment exacerbates immune senescence and consequent chronic inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
生物には最適な状況を維持する普遍的なメカニズムがあり、その一つが体内時計による生体リズムによる恒常性維持機構です。単に睡眠覚醒リズムや自律神経リズムなどを生み出す仕組みというよりは、全身の細胞の代謝秩序など生命維持に必須の原理を担うメカニズムが体内時計です。不規則な生活による恒常性破綻の原理解明のため、本研究では環境（明暗周期）の撹乱が様々な疾患発症を再現する動物モデル系を構築しました。本研究により、交替勤務などによる健康問題の本格的な予防法開発が可能になります。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] The clock modulator Nobiletin mitigates astrogliosis-associated neuroinflammation and disease hallmarks in an Altzheimer's disease model.2022
Author(s)
4.Wiroanto M, Wang C-Y, Kim E, Koike N, Gomez-Gutierrez R, Nohara K, Escobedo Jr G, Choi JM, Han C, Yagita K, Jung SY, Soto C, Lee HK, Morales R, Yoo S-H, Chen Z.
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Journal Title
FASEB J.
Volume: 36
Issue: 3
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice2020
Author(s)
Inokawa Hitoshi, Umemura Yasuhiro, Shimba Akihiro, Kawakami Eiryo, Koike Nobuya, Tsuchiya Yoshiki, Ohashi Munehiro, Minami Yoichi, Cui Guangwei, Asahi Takuma, Ono Ryutaro, Sasawaki Yuh, Konishi Eiichi, Yoo Seung-Hee, Chen Zheng, Teramukai Satoshi, Ikuta Koichi, Yagita Kazuhiro
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 2569-2569
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma2019
Author(s)
Inoue M, Tsuchiya Y, Koike N, Umemura Y, Inokawa H, Togashi Y, Maniwa J, Higashi M, Fumino S, Tajiri T, Yagita K
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Journal Title
Pediatric Surgery International
Volume: 35
Issue: 12
Pages: 1403-1411
DOI
Related Report
Peer Reviewed / Open Access
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