SIRT3 reverses aging-associated degeneration.
SIRT3 reverses aging-associated degeneration.
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DOI：
10.1016/j.celrep.2013.01.005
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发表时间：
2013-02-21
期刊：
影响因子：
8.8
通讯作者：
Chen D
中科院分区：
文献类型：
--
作者：
Brown K;Xie S;Qiu X;Mohrin M;Shin J;Liu Y;Zhang D;Scadden DT;Chen D
Sirtuins可以延长各个物种的寿命，尽管它在线虫和果蝇中的作用存在争议。sirtuins是否可以逆转衰老相关的变性尚不清楚。组织特异性干细胞在整个生命周期中持续存在，以修复和维持组织，但它们的自我更新和分化潜力随着衰老而变得失调。我们表明，SIRT3，哺乳动物sirtuin，调节线粒体蛋白的全球乙酰化景观和减少氧化应激，是高度富集在造血干细胞（HSC），它调节应激反应。SIRT3在体内平衡条件下在年轻时对HSC维持和组织体内平衡是必需的，但在应激或老年时是必需的。重要的是，SIRT3随着衰老而受到抑制，并且老化HSC中的SIRT3上调提高了它们的再生能力。我们的研究阐明了在衰老过程中控制干细胞和组织维持的线粒体稳态的可塑性，并表明衰老相关的变性可以通过sirtuin逆转。
Sirtuins extend lifespan across species, although the role in nematodes and fruitflies is controversial. Whether sirtuins can reverse aging-associated degeneration is unknown. Tissue-specific stem cells persist throughout the entire lifespan to repair and maintain tissues, but their self-renewal and differentiation potential become dysregulated with aging. We show that SIRT3, a mammalian sirtuin that regulates the global acetylation landscape of mitochondrial proteins and reduces oxidative stress, is highly enriched in hematopoietic stem cells (HSCs) where it regulates a stress response. SIRT3 is dispensable for HSC maintenance and tissue homeostasis at a young age under homeostatic conditions, but is essential under stress or at an old age. Importantly, SIRT3 is suppressed with aging, and SIRT3 upregulation in aged HSCs improves their regenerative capacity. Our study illuminates the plasticity of mitochondrial homeostasis controlling stem cell and tissue maintenance during the aging process, and shows that aging-associated degeneration can be reversed by a sirtuin.
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影响因子：
64.8
作者：
Burnett, Camilla;Valentini, Sara;Cabreiro, Filipe;Goss, Martin;Somogyvari, Milan;Piper, Matthew D.;Hoddinott, Matthew;Sutphin, George L.;Leko, Vid;McElwee, Joshua J.;Vazquez-Manrique, Rafael P.;Orfila, Anne-Marie;Ackerman, Daniel;Au, Catherine;Vinti, Giovanna;Riesen, Michele;Howard, Ken;Neri, Christian;Bedalov, Antonio;Kaeberlein, Matt;Soti, Csaba;Partridge, Linda;Gems, David
通讯作者：
Gems, David
影响因子：
64.5
作者：
Kiel, MJ;Yilmaz, ÖH;Morrison, SJ
通讯作者：
Morrison, SJ
影响因子：
29
作者：
Qiu, Xiaolei;Brown, Katharine;Chen, Danica
通讯作者：
Chen, Danica
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
64.8
作者：
Finkel T;Deng CX;Mostoslavsky R
通讯作者：
Mostoslavsky R