Functional roles of FGF23/alpha-Klotho system in the regulation of aging in the hypothalamus

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04035
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Wakayama Medical University
• Principal Investigator: Komori Tadasuke 和歌山県立医科大学, 医学部, 准教授 (90433359)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 視床下部 / FGF23 / αKlotho / 老化 / SASP

Outline of Final Research Achievements

Senescence-associated secretory phenotype (SASP) factors, such as inflammatory cytokines (TNF-α and IL-1β) and chemokines (CXCL1 and CXCL2), are known to promote several age-related diseases, including neurodegenerative disorders, cardiovascular diseases, diabetes, and cancer. However, the relationships between αKlotho and SASP factor remain unclear. The expressions of TNF-α and IL-1β were decreased by fasting in the hypothalamus of wild-type mice, but not in heterozygous αKlotho-deficient mice. In addition, CXCL1 and CXCL2 was increased in the hypothalamus of heterozygous αKlotho-deficient mice compared with that in wild-type mice. These results suggest that αKlotho is important to modulate SASP factors in the hypothalamus.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

抗老化遺伝子であるαKlothoの発見により様々な個体の老化メカニズムが明らかとなってきたが、炎症性変化などの細胞老化随伴分泌現象（SASP）とαKlothoとの関連性は不明であった。本研究により、αKlothoが視床下部における炎症性変化などSASP因子の制御に重要であることが示唆された。これらの結果は、αKlothoの新たな機能の発見に加え、中枢神経系における老化関連疾患の分子基盤の解明、及び視床下部を介した個体の老化メカニズムの解明へと繋がることが期待される。