オートファギーは,若い幹細胞と古い幹細胞の代謝と機能を維持する

Theodore T Ho¹, Matthew R Warr¹, Emmalee R Adelman²

¹Department of Medicine, Hem/Onc Division, The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143, USA.

Nature

|February 28, 2017

まとめ

オートファギーはミトコンドリアをクリアすることで幹細胞を維持し,年齢とともに造血幹細胞の再生を保ちますオートファギーの喪失は代謝を活性化し幹細胞の機能を損なうことで老化を加速します

科学分野:

ゲロントロジー
幹細胞生物学
細胞の代謝

背景:

高齢化により,血液形成幹細胞 (HSC) の再生能力が低下し,病気に繋がります.
細胞のリサイクルプロセスであるオートファギーは HSC の健康と長寿を維持するために不可欠です
代謝ストレスがHSCの機能と自己再生に大きく影響する.

研究の目的:

HSCの老化と再生におけるオートファギーの役割を調査する.
オートファジーがHSCの代謝と機能に影響を与えるメカニズムを解明する.
高齢者におけるHSC再生能力を維持するための戦略を特定する.

主な方法:

HSCの標的型自己消化欠乏症のマウスモデル
ミトコンドリア含量と代謝活動測定
HSCのエピジェネティック分析
長期的な幹細胞再生検査

主要な成果:

HSCにおける自閉性の喪失は,ミトコンドリアの蓄積と活性化された代謝状態につながる.
オートファギーの障害は骨髄分化が加速し,HSCの自己再生と再生が低下する.
高オートファギーを有する老 HSC のサブセットは静止状態と低代謝状態と再生能力を維持する.
オートファギーは,健康なミトコンドリアをクリアし,茎性を維持することによって,HSCの代謝を積極的に抑制する.

結論:

オートファギーは,HSCの代謝を抑制し,老化中に茎と再生能力を維持するために不可欠です.
HSC機能の年齢関連の低下を緩和するには,オートファギーの維持が不可欠です.
高齢者におけるHSC再生を促進するための治療戦略として,オートファギーをターゲットにすることがあります.

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