Elucidation of the mechanisms underlying in vivo carcinogenesis by comprehensive analyses of cellular senescence

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H01398
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Tumor biology
• Research Institution: The University of Tokyo
• Principal Investigator: Nakanishi Makoto 東京大学, 医科学研究所, 教授 (40217774)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 細胞老化 / p53 / シングルセル解析 / 個体老化

Outline of Final Research Achievements

We found that there are many protein aggregates in lysosomes during senescence induction. These aggregates triggers activation of CaMKII-p38MAPK-IL-1 alpha-NF-kB axis, leading to the induction of SASP. Survival of senescent cells depends on activation of glutaminolysis and its inhibition induces mortality specifically in senescent cells. We develop mouse model in which senescent cells are visualized and can be analyzed at a single cell level. We also develop mouse model in which senescence induction can be regulated. Interestingly, aging process appears to be accelerated in these mouse after induction of senescence.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究により老化細胞特異的な除去技術のシーズが開発された。この技術により個体レベルで加齢性変化を改善することができた。現在日本は超高齢社会を迎えて加齢性変化を改善する技術が社会実装されれば社会全体に大きな貢献を果たすことは間違いない。