Elucidation of the relationship between aberrant nucleic acid metabolism and accelerated aging in Werner syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15682
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Chiba University
• Principal Investigator: Kato Hisaya 千葉大学, 医学部附属病院, 助教 (90841974)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 早老症 / 老化 / ウェルナー症候群 / iPS細胞 / 核酸代謝 / 細胞老化

Outline of Final Research Achievements

The aim of this study was to elucidate the relationship between premature aging symptoms and metabolic abnormalities in Werner syndrome (WS) by revealing the metabolomic expression profile in WS. To date, we have established iPS cell lines from somatic cells of eight WS patients by introducing the Yamanaka four factors, and we have established iPS cell lines with the WRN gene, the causative gene, repaired using CRISPR/Cas9 (Kato H. Stem Cell Res. 2021). By inducing these cells to differentiate into MSCs and by further analysis, it has become clear that abnormalities in nucleic acid metabolism in WS impact premature aging phenotypes. We aim to further develop our understanding of the pathology and potential therapeutic approaches in WS.

Free Research Field

老化

Academic Significance and Societal Importance of the Research Achievements

本研究ではWSの核酸代謝異常が早期老化症候に与える影響を初めて明らかにした。WSは種々の老化関連代謝疾患を合併するため、WSにおける代謝物の変化を探求することは、老化そのものへの理解につながると考えられ、今後、一般老化と共通する新規老化機序の解明並びに抗老化治療開発への足がかりとなると期待される。