Investigation of the molecular mechanism underlying aging based on epigenome alterations in intestinal epithelial stem cells

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K13051
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Keio University
• Principal Investigator: SAITO Yoshimasa 慶應義塾大学, 薬学部(芝共立), 准教授 (90360114)
• Co-Investigator(Renkei-kenkyūsha): SATO Toshiro 慶應義塾大学, 医学部, 准教授 (70365245) ; KANAI Yae 慶應義塾大学, 医学部, 教授 (00260315) ; YAMAMOTO Naoki 慶應義塾大学, 理工学部, 准教授 (40513289)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 老化 / 加齢 / エピゲノム変化 / 腸管上皮幹細胞 / オルガノイド培養

Outline of Final Research Achievements

To understand the molecular mechanism underlying aging, we established intestinal epithelial organoids derived from both young and aged mice and investigated gene expression profiles and epigenome alterations. We found that cell proliferation and tissue formation were significantly inhibited in intestinal epithelial organoids derived from aged mice. In addition, epigenetic modifications including suppression of Lgr5 by trimethylation of histone H3 lysine 27 induced suppression of Wnt signaling. These findings indicate that epigenome alterations may lead to disabilities of cell proliferation and tissue formation during the process of aging.

Free Research Field

消化器病学