Role of RECQL5 in regulation of lipid metabolism in novel Werner's syndrome model mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16538
• 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: National Center for Geriatrics and Gerontology
• Principal Investigator: Shibuya Shuichi 国立研究開発法人国立長寿医療研究センター, 研究所 老化ストレス応答研究プロジェクトチーム, 研究員 (70866342)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 早老症 / ヘリカーゼ / 脂質代謝 / 細胞老化

Outline of Final Research Achievements

WRN/RECQL5 double-deficient mice we generated as a novel model of Werner's syndrome (WS) exhibited abnormal lipid metabolism accompanied by hyperinsulinemia similar to WS. In visceral adipose tissue, the expression of senescence-related genes increased in addition to lipid metabolism-related genes, suggesting the accumulation of senescent cells. Removal of senescent cells improved dyslipidemia in the double-deficient mice. These results suggest that double deletion of WRN and RECQL5 causes dyslipidemia caused by the accumulation of senescent cells. In addition, we found a relationship between dyslipidemia and function of skeletal muscle in sarcopenic obesity, which is a characteristic of WS.

Free Research Field

老年医学

Academic Significance and Societal Importance of the Research Achievements

本研究で、WRNとRECQL5の2重欠失は老化細胞の蓄積に起因する脂質代謝異常を引き起こすことが明らかとなった。WS患者においても様々な組織に蓄積した老化細胞が老化病態を引き起こすと考えられる。本研究の成果は老化細胞を標的としたWSの新たな治療戦略へ応用できる可能性がある。また我々が作出したWrn/Recql5 2重欠損マウスは新規WSモデルマウスとしてWSの研究発展に寄与する。