Biochemical effects of SIRT1 activators.
Biochemical effects of SIRT1 activators.
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DOI：
10.1016/j.bbapap.2009.10.025
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Baur JA
中科院分区：
文献类型：
--
作者：
Baur JA
SIRT1是最接近哺乳动物的同源酶，在低等生物中延长生命。其在哺乳动物中的作用尚不完全清楚，但包括通过其烟酰胺腺嘌呤二核苷酸（NAD+）依赖性脱乙酰酶活性调节至少34种不同的靶标。最近使用小分子激活剂和基因工程小鼠的实验为这种酶在哺乳动物生物学中的作用提供了新的见解，并有助于突出一些潜在的相关目标。最广泛使用的激活剂是白藜芦醇，这是一种小多酚，可以改善胰岛素敏感性和血管功能，提高耐力，抑制肿瘤形成，并改善与肥胖相关的小鼠早期死亡率。这些作用中的许多与SIRT 1靶点的调节一致，例如PGC1α和NFκB，然而，白藜芦醇也可以激活AMPK，抑制环加氧酶，并影响多种其他酶。一种新的激活剂，SRT 1720，以及各种方法来操纵NAD+代谢，正在成为增加SIRT 1活性的替代方法，并在许多情况下重现白藜芦醇的作用。目前，需要进一步的研究来更直接地测试SIRT1在介导白藜芦醇有益作用中的作用，评估SIRT1激活的其他策略，并确认SIRT1在体内相关的特异性靶点。鉴于SIRT1激活剂正在进入人体临床试验，并且含有白藜芦醇的“营养”制剂已经广泛使用，这些努力尤其重要。
SIRT1 is the closest mammalian homologue of enzymes that extend life in lower organisms. Its role in mammals is incompletely understood, but includes modulation of at least 34 distinct targets through its nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase activity. Recent experiments using small molecule activators and genetically engineered mice have provided new insight into the role of this enzyme in mammalian biology and helped to highlight some of the potentially relevant targets. The most widely employed activator is resveratrol, a small polyphenol that improves insulin sensitivity and vascular function, boosts endurance, inhibits tumor formation, and ameliorates the early mortality associated with obesity in mice. Many of these effects are consistent with modulation of SIRT1 targets, such as PGC1α and NFκB, however, resveratrol can also activate AMPK, inhibit cyclooxygenases, and influence a variety of other enzymes. A novel activator, SRT1720, as well as various methods to manipulate NAD+metabolism, are emerging as alternative methods to increase SIRT1 activity, and in many cases recapitulate effects of resveratrol. At present, further studies are needed to more directly test the role of SIRT1 in mediating beneficial effects of resveratrol, to evaluate other strategies for SIRT1 activation, and to confirm the specific targets of SIRT1 that are relevant in vivo. These efforts are especially important in light of the fact that SIRT1 activators are entering clinical trials in humans, and “nutraceutical” formulations containing resveratrol are already widely available.
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DOI：
10.1073/pnas.0403493101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Bauer, JH;Goupil, S;Helfand, SL
通讯作者：
Helfand, SL
影响因子：
6.1
作者：
Chan, WK;Delucchi, AB
通讯作者：
Delucchi, AB
DOI：
10.1161/atvbaha.107.155762
发表时间：
2007-12-01
影响因子：
8.7
作者：
Ceolotto, Giulio;Gallo, Alessandra;Avogaro, Angelo
通讯作者：
Avogaro, Angelo
影响因子：
29
作者：
Banks AS;Kon N;Knight C;Matsumoto M;Gutiérrez-Juárez R;Rossetti L;Gu W;Accili D
通讯作者：
Accili D
影响因子：
5.2
作者：
Almeida, Luis;Vaz-da-Silva, Manuel;Soares-da-Silva, Patricio
通讯作者：
Soares-da-Silva, Patricio