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TERTの活性化は,DNAメチル化と複数の老化の特徴を標的とする.

Hong Seok Shim1, Jonathan Iaconelli2, Xiaoying Shang1

  • 1Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell
|June 22, 2024
PubMed
まとめ

テロメラーゼ逆転写酵素 (TERT) の低活性が老化を誘発する. 新しい化合物はTERTを活性化し,テロメアの合成を促進し,細胞とマウスの老化徴候を毒性なく減少させます.

キーワード:
大人の神経生成認知能力エピジェネティクス炎症p16 (INK4a) について衰えることテロメラーゼテロメア

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科学分野:

  • 分子生物学
  • ゲロントロジー
  • 生物化学

背景:

  • テロメア縮小とテロメラーゼ逆転写酵素 (TERT) の活性低下は,老化および年齢関連の疾患と関連しています.
  • TERTはテロメア維持と老化過程における転写共同調節剤として二重の役割を果たします.

研究 の 目的:

  • TERT転写を活性化する化合物を特定し,特徴づけること.
  • TERTの活性化による老化特征および関連する病変の緩和における治療の可能性を評価する.

主な方法:

  • MEK/ERK/AP-1信号経路を調節するTERTアクティベーター化合物 (TAC) の特定
  • TERTレベル,テロメア合成,細胞老化,炎症マーカーのTAC効果の評価
  • 神経炎症,神経生成,および認知機能に対するTACのインパクトの評価 in vivo.

主要な成果:

  • TACは,ヒトの原始細胞と老いたマウスのTERT転写とテロメア合成を向上させました.
  • TAC治療は,細胞老化,炎症性サイトカインを減少させ,DNMT3B媒介によるp16INK4a発現を静止させました.
  • 脳では,TACは神経炎症を緩和し,神経栄養因子を強化し,神経生成を刺激し,毒性を誘発せず,がんリスクを増加させずに認知機能を維持しました.

結論:

  • 生理学的TERTの活性化は 複数の老化の特徴と戦うための有効な戦略です
  • 特定されたTERT活性化剤は,年齢に関連する疾患の治療と健康的な老化を促進する臨床前効果を示しています.