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2020 Fiscal Year Final Research Report

Elucidation of Aging Mechanisms by Regulation of NAD+ and Epigenome and Development of New Anti-Aging Interventions

Research Project

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Project/Area Number 19K22818
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionKeio University

Principal Investigator

Saito Yoshimasa  慶應義塾大学, 薬学部(芝共立), 教授 (90360114)

Co-Investigator(Kenkyū-buntansha) 金井 弥栄  慶應義塾大学, 医学部(信濃町), 教授 (00260315)
Project Period (FY) 2019-06-28 – 2021-03-31
Keywords老化 / NAD+ / エピゲノム / オルガノイド / 抗加齢
Outline of Final Research Achievements

To elucidate the molecular mechanism of aging, we established organoids from the intestinal epithelium of aging mice and analyzed gene expression changes and epigenomic changes.
The organoids from aged mice showed reduced proliferative capacity and tissue building ability. In addition, epigenomic changes led to decreased gene expression of stem cell markers such as Lgr5 and Wnt signaling pathway in organoids from aged mice. In addition, administration of nicotinamide mononucleotide (NMN), an NAD+ precursor, changed the morphology of intestinal epithelial organoids from aged mice to that of young mice and restored the expression of stem cell-related genes, suggesting that NMN increases NAD+ activity and has an anti-aging effect.

Free Research Field

抗加齢医学

Academic Significance and Societal Importance of the Research Achievements

本研究により特定された加齢特異的なエピゲノム変化や遺伝子発現変化およびニコチンアミドモノヌクレオチド(NMN)などのNAD+の前駆体の投与による変化をさらに詳細に検討することで、老化の分子メカニズムを解明すると共に新たな抗加齢介入の基盤が開発されることが期待される。
開発に成功すれば、高齢者の健康寿命の延長ならびにQOLの向上が実現し、がんをはじめとする加齢関連疾患の予防や高齢者の臓器移植の成功率向上などにつながることが期待される。最終的には、高齢者における医療費や介護負担の軽減にもつながり、現在我が国において大きな問題となっている医療経済の改善にも大きく貢献することが期待される。

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Published: 2022-01-27  

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