Effects of Melatonin Brain Metabolites on Restoring Age-Related Long-Term Memory Impairment and its Application to Human Health Foods

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K11016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: HATTORI Atsuhiko 東京医科歯科大学, 教養部, 教授 (70183910)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: AMK / AFMK / メラトニン / 記憶力改善 / 加齢 / 物体認識試験 / マウス / 食品

Outline of Final Research Achievements

Melatonin, which has attracted attention as an anti-aging hormone, is metabolized in the brain mainly through N-acetyl-N-formyl-5-methoxykynuramine (AFMK) to N-acetyl-5-methoxykynuramine (AMK). Therefore, we investigated the effects of melatonin, AFMK and AMK on learning and memory in mice and found that AMK has a strong long-term memory-inducing effect. In addition, when the effects of AMK were tested in aged mice, whose long-term memory formation ability had declined due to aging, it was found that a single administration of AMK was sufficient to restore the reduced memory ability, which was reported in 2021 in the Journal of Pineal Research, the world's leading international scientific journal in the field of physiology. Another objective of this research is to lay the foundation for its deployment in humans. To this end, the melatonin , AFMK, and AMK contents were determined in over 150 foodstuffs using LC/MS/MS.

Free Research Field

抗加齢医学

Academic Significance and Societal Importance of the Research Achievements

高齢者の記憶力の低下は、本人だけでなく社会全体のQOLの低下につながるため、その予防や改善のための薬物や機能性食品の開発は喫緊の課題である。メラトニンは、「夜の時刻情報の伝達物質」として生体リズム(睡眠相)を制御する作用が知られ、現在、睡眠改善薬としても利用されている。本研究では、メラトニンが脳内で代謝されてできるAMKに長期記憶誘導効果があることを見出し、老齢マウスにおいても低下した記憶能力を回復させることを見出した。この結果は、今後この研究を進めることで、超高齢社会における高齢者の認知機能改善に寄与できるものと思われる。