Human skin rejuvenation by removal of cells causing SASP

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19589
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
• Research Institution: Keio University
• Principal Investigator: Kishi Kazuo 慶應義塾大学, 医学部(信濃町), 教授 (40224919)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: SASP / 老化細胞 / 若返り

Outline of Final Research Achievements

In this study, we searched for markers that specifically label senescent cells by comparing genes expressed in cellular senescence models and normal human fibroblasts by RNA-seq. We narrowed our focus to factors expressed on the surface of fibroblast cell membranes, and isolated and identified that the proteins encoded by these genes are actually on the cell membrane surface. Antibodies to the target molecules were conjugated with a light-sensitive substance and confirmed by immunoprecipitation. The antibody was used to confirm whether or not light exposure can kill cells, and it was confirmed that young cells showed little cell death, but senescent cells induced a lot of cell death.

Free Research Field

抗加齢医学

Academic Significance and Societal Importance of the Research Achievements

加齢に関連する疾患の発症には老化した細胞の蓄積が関与することから、抗加齢医療において生体から老化細胞を除去する治療法(senolysis)の開発が注目を集めてきた。皮膚においても老化細胞の除去は、SASPの悪影響を除去し、細胞外マトリックスの正常化、脂肪細胞の分化促進、炎症の軽減、および皮下構造の回復を介して老化の表現型を改善すると考えられた。本研究では、皮膚の老化に関与する老化線維芽細胞のみに特異的なマーカー分子を探索し、これを標的とした光免疫療法（Photoimmunotherapy; PIT）を用いた新しいアプローチのsenolysisを開発することで、有用な抗老化治療開発を目指した。