NAD(+) /Sirtuin経路は,ミトコンドリアのUPRとFOXOシグナリングの活性化を通じて長寿を調節する
Laurent Mouchiroud1, Riekelt H Houtkooper, Norman Moullan
1Laboratory for Integrative and Systems Physiology, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland.
Cell
|July 23, 2013
まとめ
減少したNAD (((+) は,老化と寿命に影響を与えます. ワームのNAD (((+) レベルを回復することは,ストレス反応経路を活性化することによって長寿を促進し,年齢に関連する衰退のための治療目標を示唆します.
科学分野:
- バイオケミストリー バイオケミストリー
- ゲロントロジーはゲロントロジーの学科です.
- 分子生物学は分子生物学である.
背景:
- ニコチナミドアデニン・ディヌクレオチド (NAD(+)) は,代謝恒常化の重要なコファクターであり,シルトゥイン酵素の重要な基質である.
- NAD ((+) レベルが年齢に関連して低下することは,マウスやCaenorhabditis elegans.を含む様々な生物で観察されています.
- 減少したNAD (((+) レベルは,寿命の短縮と代謝機能障害に関連しています.
研究 の 目的:
- 老化と長寿におけるNAD (((+) の役割を調査する.
- 年齢に関連した代謝低下とCaenorhabditis elegansの寿命に対するNAD (((+) レベルを調節する効果を決定する.
- NAD (((+)) 媒介による長寿の背後にある分子メカニズムを解明する.
主な方法:
- 若いマウスと老いたマウスとワームのNAD (((+) 濃度の比較分析.
- ワームのNAD+レベルを回復させるための遺伝子操作と薬理学的介入.
- 寿命,代謝パラメータ,および分子シグナル伝達経路の評価 (sir-2.1,UPR,mt,DAF-16).
主要な成果:
- NAD (((+) レベルは,マウスとワームの年齢とともに低下します.
- NADを低下させると,高齢化による寿命の縮小が悪化する.
- NAD (((+) の回復は代謝の低下を防止し,ワームの寿命を延ばします.
- これらの有益な効果は,サーチューインsir-2.1. に依存しています.
- NAD (((+) 回復は,ミトコンドリアの展開タンパク質応答 (UPR (((mt)) とDAF-16/FOXOシグナル伝達を含むミトコンドリアのストレス反応を活性化します.
結論:
- NAD (((+) レベルは,老化と長寿の重要な調節因子です.
- NAD ((+) レベルを上昇させることで,年齢に関連した代謝の低下を抑制し,寿命の延長を促進することができます.
- NAD (((+) レベルを調節し,ミトコンドリアのストレスシグナル伝達経路を活性化することは,年齢関連の疾患に対する潜在的な治療戦略です.
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