2021 Fiscal Year Final Research Report

Regulation mechanisms of chronic inflammation mediated by characteristic glycans associated with extreme human longevity

Research Project

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Project/Area Number	19K11736
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 Metropolitan Geriatric Hospital and Institute of Gerontology
Principal Investigator	Miura Yuri 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究副部長 (00216574)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	健康長寿 / 糖鎖 / グライコプロテオミクス / 血漿タンパク質 / 長期縦断コホート / 慢性炎症 / 質量分析 / 老化
Outline of Final Research Achievements	The purpose of this study was to clarify the biological significance of N-glycans associated with successful aging, and the mechanisms of healthy aging. We performed the observational study using a longitudinal cohort study for elderly people, and the validation study using genetically modified animals. In observational study, we examined the characteristic altered N-glycopeptides associated with diabetic cognitive impairment, and indicated that multi-branched and highly sialylated glycans, which were associated with successful aging, were decreased. In semi-super centenarians (SSCs) who are considered to accomplish successful aging, it was reported that diabetes was very rare and that age-related cognitive impairment was suppressed. Accordingly, these results might suggest that N-glycans associated with successful aging emerged in SSCs not as a result of extremely senescence, but as a factor of successful aging such as the suppression of age-related cognitive impairment.
Free Research Field	プロテオミクス・グライコミクス
Academic Significance and Societal Importance of the Research Achievements	本研究では健康長寿糖鎖の生物学的な意義を明らかにするため、長期縦断調査を用いた観察研究と糖鎖リモデリングマウスを用いた検証研究を行うことを目的とした。長期縦断調査を用いたグライコプロテオミクスにより、糖尿病性認知機能低下において健康長寿糖鎖が減少する傾向にあることを明らかにし、健康長寿糖鎖が認知機能の維持など健康長寿の「要因」に関連する可能性を示唆した。現在進行中の慢性炎症に関する観察研究や糖鎖リモデリングマウスを用いた検証研究により、さらに健康長寿糖鎖の健康長寿達成への寄与が明らかになれば、これらの糖鎖をバイオマーカーとする高齢者の健康管理システム開発に発展することが期待される。