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発達ROSは,生物のストレス抵抗性と寿命を個別化します

Daphne Bazopoulou¹, Daniela Knoefler¹, Yongxin Zheng^2,3

¹Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.

|December 6, 2019

まとめ

C. elegansの早期活性酸素種 (ROS) は,ヒストンH3K4me3レベルを低下させることで,ストレス耐性を高め,寿命を延ばします. このエピジェネティックの変化はレドックス・ホメオスタシスと長寿を高めます

科学分野:

老化に関する研究
エピジェネティクス
細胞リドックスホメオスタシス

背景:

寿命の個性の起源を理解することは老化に関する研究において極めて重要です
反応性酸素種 (ROS) は,発達と老化に複雑な役割を果たします.

研究の目的:

生後初期における ROS,表遺伝的変異,寿命の決定との関連を調査する.
ROS誘発のストレス抵抗と長寿を媒介するヒストンH3K4me3の役割を調査する.

主な方法:

発達研究のためのモデル生物として Caenorhabditis elegans を利用した.
哺乳類の細胞培養実験に HeLa 細胞を使用した.
エピジェネティック変異に関与する重要な酵素を特定するために,in vitro試験を行った.

主要な成果:

C. elegansの亜集団の早期発達の過程でROSが一時的に増加すると,寿命が延びた.
この寿命延長は,ROS媒介による発達ヒストンH3K4me3レベルの全般的な低下と関連していました.
H3K4me3濃度の減少は,C. elegansと哺乳類の細胞培養の両方でストレス抵抗性を高めました.
SET1/MLLヒストンメチルトランスフェラーゼは,COMPASS複合体の酸化還元素敏感成分として特定されました.

結論:

ストレス耐性や長寿をエピジェネティックにプログラムすることができます
ROSに敏感なエピジェネティックマーク,特にH3K4me3レベルは,寿命を調節する重要な媒介です.
発見は,一時的な発達のROS,表遺伝的変化,そして老化の結果との間の新しいリンクを示唆する.

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