Elucidation of metabolic network in cellular senescence using next-generation proteomics.

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Niigata University
• Principal Investigator: Oshikawa Kiyotaka 新潟大学, 医歯学系, 准教授 (50380051)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 細胞老化 / プロテオミクス

Outline of Final Research Achievements

In this research project, we established three types of senescent cell lines (telomere shortening, oncogene-induced senescence, and oxidative stress-induced senescence) and measured protein abundance of metabolic enzymes using iMPAQT system. We found that DNA synthesis-related enzymes are commonly down-regulated in these cell lines. Down-regulation of ribonucleotide reductase catalytic subunit M1 (RRM1) in normal cells were growth arrest and resulted in a premature senescence-like phenotype (SA-β-Gal staining positive, up-regulation of p16 and p21 expression, and down-regulation of Lamin B1 expression).
These results indicate that cellular senescence is caused by down-regulation of RRM1 expression.

Free Research Field

基礎生物学

Academic Significance and Societal Importance of the Research Achievements

老化細胞は増殖細胞とは異なった代謝状態を取ることが知られているが、これまでにさまざまな老化細胞の代謝ネットワークを対象にした解析例はほとんどない。加えてDNA合成関連酵素が直接、細胞老化を制御しているという報告は国内外において、あまり見当たらない。
本研究により解明された細胞老化における代謝システムの分子機構は、老化研究において新たなメカニズムを理解する上で非常に重要であると考えられる。