2021 Fiscal Year Final Research Report
The elucidation of the mechanism by which intestinal epithelial cells affect impaired glucose tolerance during aging
| Project/Area Number |
19K09017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | SIRT1 / 細胞老化 |
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| Outline of Final Research Achievements |
We clarified that the increase of SIRT1 activity by fasting regulates Neurogenin3 expression and the number of intestinal endocrine cells through the deacetylation of β-catenin and the cell cycle arrest in intestinal endocrine progenitor cells. These revealed a novel mechanism for controlling intestinal endocrine differentiation by fasting. On the other hand, our data suggest that cellular senescence in the intestine regulates glucose and bile acid absorption and hepatic gluconeogenesis. The mechanism of glucose intolerance in the elderly has been partly clarified.
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| Free Research Field |
老化
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| Academic Significance and Societal Importance of the Research Achievements |
腸管は栄養素吸収やホルモン分泌を通じ、代謝に重要な役割を果たす臓器であるが、これまで腸管を軸とした加齢現象の制御は報告されていない。本研究では、腸管ホルモンや腸管上皮の細胞老化の高齢者耐糖能障害への影響を明らかにすることにより、加齢に伴う耐糖能障害を制御する方法開発の基盤を構築することを目的とした。加齢による腸管内分泌細胞や腸管上皮の変化についての新しい知見を得ることができただけでなく、腸管を起点とする加齢に関わる臓器間ネットワークの存在が示唆され、老化研究に新しい展開をもたらすことが期待される。
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