Investigation of the relationship between circadian clock disorders and inflammation

• Project/Area Number: 17KT0129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Yasuhiro Umemura 京都府立医科大学, 医学(系)研究科(研究院), 助教 (40612734)
• Project Period (FY): 2017-07-18 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 体内時計 / 炎症 / 生理学 / 脳神経疾患 / 発現制御 / 免疫学

Outline of Final Research Achievements

In the present study, we subjected adult wild-type mice to distinct chronic jet-lag paradigms, 8-hour phase advance every 4 days or 8-hour phase delay every 7 days,to induce non-adjustive and adjustive phase shifts in the behavior. The non-adjustive for the circadian clock cause long-term circadian misalignment in the mice and the mice had significant early mortality, which is consistent with our previous study. These non-adjustive mice exhibited the disrupted circadian rhythm. The RNA sequencing analysis showed the activation of immune system and immune disease related signaling pathways in the liver and kidney. Our results underscore immune homeostasis as a pivotal intervention target against clock-related disorders in a lot of shift workers.

Academic Significance and Societal Importance of the Research Achievements

体内時計は、生命維持に必須の生理機能である。その体内時計と社会リズムとの間の齟齬が、様々な健康問題を引き起こしている。本研究では、マウスの飼育環境の光条件を頻繁に変更して、マウスの活動時間を変える条件での飼育を行った。各条件での飼育を長期間飼育した結果、光同調ができないような光条件では、早期死亡個体が多く、寿命の短縮傾向が見られた。これらのマウスの肝臓と腎臓において、老化促進や慢性炎症を示す所見が得られた。これらはシフトワーカーの健康問題としてあげられる様々な疾患と相関があることが知られているおり、全身性の病態を引き起こす病因として成立するのか今後さらに検討する。

Research Products

• [Journal Article] Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice (2020)
  • 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
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 2569-2569
  • DOI: 10.1038/s41598-020-59541-y
  • NAID: 120006799241
  • Peer Reviewed / Open Access / Int'l Joint Research