Roloes of cellular senescence in pulmonary disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: SUGIMOTO Masataka 国立研究開発法人国立長寿医療研究センター, 老化機構研究部, 室長 (50426491)
• Research Collaborator: SATO Tadashi ; SUGIMOTO Kazushi ; KANAYAMA Kazuki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 細胞老化 / 老化 / 肺 / 呼吸器疾患 / 肺気腫 / モデル動物 / Senolytic薬

Outline of Final Research Achievements

Senescent cells accumulate in several tissues during aging, while its biological consequence remains unclear. In this study, we addressed the roles of cellular senescence in pulmonary aging and disease using transgenic mice of which senescent cells can be eliminated through toxin-mediated cell knockout system.
We found that the pulmonary function, which was declined in aged animals, was restored upon the elimination of senescent cells, suggesting that senescent cells contribute to the lung aging and that aging phenotypes are at least partly reversed by targeting the senescent cells.
Next, we investigated if senescent cell-dependent changes in lung tissue are involved in the development of pulmonary emphysema. We found that genetic or pharmacological elimination of senescent cells ameliorates the emphysema-associated pathologies. Together, these results strongly suggest that senescent cells are potential therapeutic target for pulmonary emphysema.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

老化細胞は加齢とともに組織中に蓄積することは古くから知られていたが、組織老化との関係については不明であった。本研究では主任研究者が独自に樹立した老化細胞除去マウスを用い、肺組織の老化と細胞老化の因果関係について初めて明らかにした。また、先進諸国では慢性閉塞性肺疾患（COPD）による死亡が増加している。本研究ではCOPDの主要病態である肺気腫モデルを用いて解析を行い、老化細胞が気腫を増悪化させる因子であること、さらに老化細胞が同疾患の有効な創薬標的であることを明らかにした。