Analysis of the mechanisms for pathogenesis of the disease caused by age-dependent dysfunction of zinc homeostasis, focusing on the expression regulation of zinc transporters and zinc status.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15262
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Kyoto University (2022-2023); Kyoto Pharmaceutical University (2021)
• Principal Investigator: Nishito Yukina 京都大学, 生命科学研究科, 特定助教 (20867709)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 亜鉛 / 輸送体 / 加齢 / ホメオスタシス / 発現制御

Outline of Final Research Achievements

Zinc is an essential trace element for various physiological function. The serum concentration of zinc gradually decreases with age, which cause cognition-related diseases and tissues inflammation. However, the molecular mechanisms underlying this is not fully understood. In this study, we examined how age-dependent dysfunction of zinc homeostasis cause several diseases, focusing on the
relationship between the expression regulation of zinc transporters and zinc status. We found that the increase expression of zinc importer ZIP4 increased cellar zinc content and the expression of zinc exporter ZNT1 in the culture cell analysis. We cannot detect the differences between these expression changes of zinc transporters and zinc status in the analysis using aged-mouse models, however, we found that the metal homeostasis was disturbed in aged-mouse, which may provide new insights into the mechanism of the pathogenesis of diseases caused by aged-dependent zinc deficiency.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

血清亜鉛値の実態調査報告によると、日本人の約3割が亜鉛欠乏状況にあることが算出されており、更に、高齢者では約8割が低亜鉛血症を引き起こしていることが報告されている。したがって、高齢化社会を迎えた日本において、亜鉛欠乏は更に深刻な問題となることが予想される。本申請課題では、加齢に伴う低亜鉛血症並びに関連疾患の発症機序を明らかとすると共に、この制御機構を標的とした亜鉛吸収効率促進因子の同定を目指している。加齢に伴う低亜鉛血症および関連疾患の予防・改善法の確立を目指す本研究は、高齢者の健康を維持することに貢献し、社会・国民へ還元できる重要課題である。