Exploring Mechanisms of Age-Related Glucocorticoid Hypersecretion

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K11651
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Teikyo University
• Principal Investigator: Adachi Mimi 帝京大学, 医学部, 教授 (10323693)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 老化 / 細胞老化 / 糖質コルチコイド / SASP / IL1b / SF1

Outline of Final Research Achievements

Recently, it has become clear that changes in an individual's function with aging are largely related to SASPs secreted by senescent cells that accumulate in various tissues. Glucocorticoids (GCs) play an important role in regulating metabolism and immune responses through glucocorticoid receptor (GR), which is present in many organ tissues. GC deregulation leads to various diseases such as metabolic and immune abnormalities, which are also common pathologies of aging-related diseases. However, the age-related changes in the secretion mechanisms of GCs were not obvious. In this study, we found that hypersecretion of GC is caused by the secretion of IL1β, one of the SASPs, from senescent cells that accumulate in the adrenal cortex, resulting in the disappearance of GC diurnal oscillation in aged mice. The novel GC hypersecretory mechanism in aged adrenal cortex could be a potential target for new aging research.

Free Research Field

加齢医学

Academic Significance and Societal Importance of the Research Achievements

本研究で発見した新規の糖質コルチコイド分泌メカニズムは、副腎皮質にとどまらず、受容体を有する多くの臓器組織に影響を及ぼすことが考えられる。したがって、GC分泌様式を若返らせることにより、GCの過分泌によって引き起こされ、また老化関連疾患でもある代謝異常などの疾患の発症および老化そのものを予防、または治療できることが期待できる。さらに広く成人疾患の治療戦略として波及することが期待される。また老化細胞がどのように、組織の老化を促進するかについて理解する上で、老化研究自体に大きな示唆を与えるものである。以上より、学術的、社会的な意義は大変大きいと思われる。