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2023 Fiscal Year Final Research Report

Role of oxidative stress in chromosomal insability with age

Research Project

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Project/Area Number 22K19283
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionTohoku University

Principal Investigator

Tanaka Kozo  東北大学, 加齢医学研究所, 教授 (00304452)

Project Period (FY) 2022-06-30 – 2024-03-31
Keywords癌 / 細胞・組織 / 染色体
Outline of Final Research Achievements

We have found that skin fibroblasts from old mice exhibit chromosomal instability, which is partly due to oxidative stress. In the present study, we aimed to clarify the effect of oxidative stress on age-related chromosomal instability. We found that oxidative stress is caused by an increase in ROS production associated with mitochondrial functional decline and that oxidative stress induces replication stress. It was also found that reducing replication stress ameliorates chromosomal instability and that excessive microtubule stabilization is the cause of chromosomal instability. Overall, we clarified the sequence of events by which oxidative stress induces chromosomal instability in old mouse cells.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

酸化ストレスと老化の関連はフリーラジカル説として提唱されていたが、本研究はこの古くからある仮説を、老化にともなう染色体不安定性と結びつけた点に意義がある。また老齢マウスから線維芽細胞を単離し、低酸素条件下のライブセルイメージングにより染色体分配を観察する手法も独自性が高い。本研究は、染色体不安定性を老化の指標の1つとして確立し、抗酸化力を高めることによりこれを改善する方策の開発につながる可能性がある。染色体不安定性から生じる染色体異数性や微小核は、遺伝子発現の異常や炎症性サイトカインの分泌などを通じてがんなど様々な病態につながる可能性があり、本研究がそれらの理解や制御に資することが期待される。

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Published: 2025-01-30  

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