幹細胞の老化 幹細胞の老化 ミトコンドリアのUPR媒介のメタボリックチェックポイントは,造血幹細胞の老化を調節する
Mary Mohrin1, Jiyung Shin1, Yufei Liu2
1Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA.
Science (New York, N.Y.)
|March 21, 2015
まとめ
老化は,メタボリックホメオスタシスを破壊することによって,幹細胞の機能を損なう. この研究では,SIRT7が検出されました.
科学分野:
- 細胞生物学 細胞生物学
- 老化に関する研究.
- ミトコンドリアの機能
背景:
- 成人幹細胞の劣化は,老化に関連した組織機能不全に大きく寄与する.
- 幹細胞のメタボリックホメオスタシスの基礎となるメカニズムは,依然としてほとんど不明である.
研究 の 目的:
- 幹細胞のメタボリックホメオスタシスを支配する規制経路を解明する.
- mitochondrial unfolded protein response (UPR) (ミトコンドリアの展開タンパク質応答 (UPR)) でSIRT7とNRF1の役割を調査する.
主な方法:
- SIRT7,NRF1,および細胞のエネルギー代謝の相互作用を調査した.
- 造血幹細胞 (HSC) の静止状態と再生能力に対するSIRT7不活性化の影響を評価した.
- 高齢なHSCにおけるSIRT7発現レベルを調べ,SIRT7アップレギュレーションの効果を評価した.
主要な成果:
- SIRT7とNRF1を含むUPRの規制部門を特定し,代謝と増殖に関連しています.
- SIRT7の不活性化により,HSCの静止状態が低下し,ミトコンドリアタンパク質の折り畳みストレス (PFS) が増加し,再生機能が低下しました.
- SIRT7発現の減少は,高齢のHSCで観察され,そのアップレギュレーションは,再生可能性を高めました.
結論:
- UPR (mt) 媒介の代謝チェックポイントの緩和は,HSCの老化における可逆的要因である.
- SIRT7は,HSCの代謝性ホメオスタシスと再生能力を維持する上で重要な役割を果たします.
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