The role of transcriptional repressor ZBTB20 on premature aging and energy metabolism

• Project/Area Number: 18K06971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Tokai University
• Principal Investigator: ISHII Takamasa 東海大学, 医学部, 准教授 (20548680)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 転写因子 / 複製ストレス / DNA損傷修復 / 代謝 / クロマチン再構築

Outline of Final Research Achievements

We have focused on the role of new age-related genes. The original new premature aging model mouse which has been established by our unique gene-trap technology (WO 2005123918 A1) has developed obesity and been short-lived with abnormal zbtb20 gene expression located in16qC1.1-3 region. It has been reported that the abnormal gene expression of zbtb20 which is located in 3q13.31 region develops primrose syndrome and 3q13 deletions and microdeletions syndrome in human. In this research, it has been clarified and suggested that the abnormal gene expression of zbtb20 develops obesity with the enhanced lipid metabolism resulting in short-lived.

Academic Significance and Societal Importance of the Research Achievements

最近、プリムローズ症候群について、原因遺伝子がzbtb20であり、３番染色体欠失症候群に確認される早老症と同様の病態を呈することが報告された。これまで他の研究グループらによって、中枢神経の発生過程におけるZBTB20転写抑制因子の役割が徐々に明らかにされてきた一方、生体成熟後のZBTB20の役割は未だ不明であった。本研究によって、ZBTB20が生体成熟後にエネルギー代謝の同化と異化を制御し、特に脂質代謝を制御していることを示唆する成果を得た。本研究成果は、生体成熟後のエネルギー代謝を制御する新たな分子機構の一端を解明し、短寿命の原因となる肥満の新たな制御法を示唆する成果となった。

Research Products

• [Journal Article] 老化メカニズムの徹底究明 分子からアンチエイジングまで Vol2. 酸化ストレス研究の現状と展望 (2021)
  • Author(s): 石井恭正，安田佳代
  • Journal Title: 別冊医学のあゆみ Volume: 2 Pages: 9-16
• [Journal Article] 老化の分子生理基盤 (2020)
  • Author(s): 石井恭正，安田佳代
  • Journal Title: Farumashia Volume: 56 Issue: 11 Pages: 989-993
  • DOI: 10.14894/faruawpsj.56.11_989
  • NAID: 130007933992
  • ISSN: 0014-8601, 2189-7026
  • Peer Reviewed
• [Journal Article] 老化研究の進歩 Vol.2 酸化ストレス研究の現状と展望 (2020)
  • Author(s): 石井恭正，安田佳代
  • Journal Title: 週刊医学のあゆみ Volume: 272 Pages: 673-680
  • NAID: 40022159769
• [Journal Article] 老化研究の進歩，酸化ストレス研究の現状と展望． (2020)
  • Author(s): 石井恭正，安田佳代
  • Journal Title: 医歯薬出版株式会社，医学のあゆみ Volume: 272 Pages: 673-680
• [Journal Article] Metabolic biomarkers in nematode C. elegans during aging. Reviews on Biomarker Studies of Metabolic and Metabolism-Related Disorders (2019)
  • Author(s): Yanase S., Ishii T., Yasuda K., Ishii N.
  • Journal Title: Adv Exp Med Biol. Volume: 1134 Pages: 163-175
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolic Biomarkers in Nematode C. elegans During Aging (2019)
  • Author(s): Y. Sumino, T. Ishii, K. Yasuda, N. Ishii
  • Journal Title: Reviews on Advances in Experimental Medicine and Biology, Biomarker Studies of Metabolic and Metabolism-Related Disorders Volume: 1134 Pages: 163-175
  • DOI: 10.1007/978-3-030-12668-1_9
  • ISBN: 9783030126674, 9783030126681
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Age-dependently chronic innate immune response with 4-hydroxy-2-nonenal in mice. (2019)
  • Author(s): Ishii T.
  • Organizer: The 35th Spring International Conference of the Korean Society for Gerontology, The 19th Korea-Japan Joint Symposium, Session 7: Aging and immunity
  • Int'l Joint Research / Invited
• [Presentation] 3q13.31欠失症候群・プリムローズ症候群に現れる老化症状：新たな早老機序に迫る． (2019)
  • Author(s): 石井恭正
  • Organizer: 第31回日本老年学会総会，第42回日本基礎老化学会大会，シンポジウムS4「幹細胞老化と加齢性疾患・早老症」
  • Invited
• [Presentation] Age-dependently chronic innate immune response with 4-hydroxy-2-nonenal in ROS-overproduced interstitial lung disease (ILD) model mice. (2019)
  • Author(s): Ishii T., Asari S., Sugita K., Yasuda K., Miyazawa M., Yamamoto J.Y., Hartman P.S. and Ishii N.
  • Organizer: Gordon Research Conference, Biology of Aging: Molecular, Cellular and Physiological Determinants of Lifespan and Healthspan
  • Int'l Joint Research
• [Presentation] 電子伝達系障害酸化ストレスに対する適応応答の加齢変化 (2018)
  • Author(s): 石井恭正
  • Organizer: 第71回日本酸化ストレス学会，第18回日本NO学会 合同学術集会
  • Invited