Functional analyses of TAF-I in regulation of cellular senescence and SASP gene transcription

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06010
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Kato Kohsuke 筑波大学, 医学医療系, 助教 (90466673)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 細胞老化 / 炎症老化 / クロマチン / ヒストンシャペロン

Outline of Final Research Achievements

The aim of this study was to elucidate the regulatory mechanism of cellular senescence by chromatin regulator TAF-I using a cellular senescence induction system in cultured cells. When TAF-I expression was suppressed in normal human fibroblasts and oncogenes were expressed to induce cellular senescence, abnormalities in the expression of inflammatory cytokine genes and in the formation of heterochromatin structures specific for cellular senescence were observed. The results also revealed that these abnormalities were caused by abnormal processing of histone H3 via suppression of expression of cathepsin L1, a protease localized in the nucleus. These results suggest that TAF-I may be involved in the regulation of gene expression associated with cellular senescence through the regulation of specific chromatin structures.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会をむかえつつある我が国において、加齢に伴う疾患や身体機能低下の予防と治療法の確立は重要な課題である。このような加齢性疾患は慢性炎症が根本的な原因と考えられており、炎症老化（inflammaging)と呼ばれている。近年、炎症老化には体内での老化細胞の蓄積が関与している可能性が示唆されており、細胞レベルでの老化とそれに伴う炎症反応活性化のメカニズムを解明することは、加齢性疾患の予防と治療法の確立において重要である。本研究はそのような細胞老化のメカニズムの一端を解明したものであり、学術的にも社会的にも意義をもつものである。