The mechanism of the aging-associated alternation of the circadian clock via a systemic pro-aging factor, beta2-microglobulin

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08518
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Ohu University (2018); Tohoku University (2016-2017)
• Principal Investigator: Moriya Takahiro 奥羽大学, 薬学部, 教授 (80298207)
• Co-Investigator(Kenkyū-buntansha): 小林 正樹 東北工業大学, 工学部, 教授 (90332981)
• Research Collaborator: KOBAYASHI Takumi ; MOGI Asuka ; TAKODA Jun ; YOSHIDA Nobuhiro ; INOUE Rika
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 老化 / 体内時計 / 視交叉上核

Outline of Final Research Achievements

It is well known that the function of the mammalian circadian clock is altered by aging. In this study, we investigated whether a systemic pro-aging factor, beta2-microglobulin is involved in aging-associated alternation of the circadian clock function in mice. We found that the administration of beta2-microglobulin induced the elongation of the period in the free-running rhythm of clock gene expression in the cultured suprachiasmatic nucleus. It also reduced the density of arginin-positive neurons and astrocytes in the suprachiasmatic nucleus. These results suggest that a systemic pro-aging factor, beta2-microglobulin is involved in aging-associated alternation of the circadian clock function in mice.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

加齢は様々な生理機能を同時多発的に変化させる性質をもつこともあり、加齢に伴う生理機能の変化を現象論的に解析せざるを得ない状況にあった。体内時計研究においても、加齢に伴う行動リズムの異常や、視交叉上核の神経ネットワーク障害など、大変意義深い研究成果が報告されているにも関わらず、その誘発因子の同定には至っていない。本研究では、すでに加齢血漿中で増加することが知られているbeta2-ミクログロブリンに着目し、体内時計機能の加齢変化の誘発因子としての可能性を検証し、これを明らかにした。さらに研究が進展すれば、加齢に伴う生体リズム障害の新しい診断方法や治療薬の開発にも貢献できる可能性が考えられる。