Elucidation of the principles of hematopoietic stem cells in aging and overcoming aging-related diseases

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16298
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Koide Shuhei 東京大学, 医科学研究所, 特任助教 (10845126)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 造血幹細胞 / 加齢 / Clusterin / 老化マーカー

Outline of Final Research Achievements

In this study, we focused on Clusterin (Clu), a novel marker of aging identified by the applicant, aiming to clarify the aging mechanism of HSCs by analyzing their reporter mice. Clu-negative aged HSCs showed high stem cell activity, whereas Clu-positive aged HSCs markedly lost their differentiation ability. Based on these results, the age-related decline in HSC function may be attributed to Clu-positive HSCs. If future intervention methods targeting Clu-positive HSCs can be established, new therapeutic strategies for aging-related diseases such as myelodysplastic syndrome are expected to be developed.

Free Research Field

血液および腫瘍内科学関連

Academic Significance and Societal Importance of the Research Achievements

先進国を中心とした高齢化の世界的進行により、健康的に生活できる期間の延伸はいまや世界各国の共通課題である。本研究により明らかとなったCluの発現変容は造血幹細胞の加齢変化を示すバイオマーカーとしての利用が期待される。今後、Cluレポーターマウスの詳細な解析から、加齢造血幹細胞の出現様式の理解が深まり、さらにClu陽性造血幹細胞を直接標的とした介入法が確立できれば、骨髄異形成症候群などの老化関連疾患への新たな治療戦略が期待される。