Metabolism, longevity and epigenetics.
Metabolism, longevity and epigenetics.
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DOI：
10.1007/s00018-013-1295-3
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发表时间：
2013-05
影响因子：
8
通讯作者：
Mostoslavsky, Raul
中科院分区：
文献类型：
--
作者：
Cosentino, Claudia;Mostoslavsky, Raul
即使在高等真核生物中，代谢稳态以及影响营养物质吸收的干预措施也是影响寿命的行之有效的手段。直到最近，解释这种效应的分子机制仍然知之甚少。 Sirtuins 代表一组蛋白质脱乙酰酶，其功能依赖于代谢中间体 NAD+ 作为辅助因子。因此，它们感知代谢压力，进而在多个层面发挥作用，以发挥适当的代谢适应作用。除此之外，sirtuins 还可以作为组蛋白脱乙酰酶诱导表观遗传变化，从而调节转录和 DNA 修复。最近的研究表明，除了去乙酰化酶之外，其他染色质修饰剂（例如组蛋白乙酰转移酶 (HAT)）的活性也可能与其中间代谢物乙酰辅酶 A 的可用性紧密相关。在这项研究中，我们将总结当前的知识，描述新兴概念，表明能够感知代谢压力的表观遗传机制、它们的适应性代谢反应及其在长寿中的潜在作用之间存在密切的串扰。
Metabolic homeostasis, as well as interventions that influence nutrients’ uptake, are well-established means to influence lifespan even in higher eukaryotes. Until recently, molecular mechanisms to explain such an effect remained scantily understood. Sirtuins represent a group of protein deacetylases that depend on the metabolic intermediate NAD+ as a co-factor for their function. For this reason they sense metabolic stress and in turn function at multiple levels to exert proper metabolic adaptation. Among other things, sirtuins could perform as histone deacetylases inducing epigenetic changes to modulate transcription and DNA repair. Recent studies indicate that beyond sirtuins, the activity of other chromatin modifiers, such as histone acetyl transferases (HATs), might also be tightly linked to the availability of their intermediate metabolite Acetyl-CoA. In this study, we will summarize current knowledge depicting emerging concepts indicating a close crosstalk between the epigenetic machineries able to sense metabolic stress, their adaptive metabolic responses and their potential role in longevity.
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DOI：
10.1126/science.1170633
发表时间：
2009-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
de Lange T
通讯作者：
de Lange T
影响因子：
10.5
作者：
Berger, Shelley L.;Kouzarides, Tony;Shilatifard, Ali
通讯作者：
Shilatifard, Ali
影响因子：
10.5
作者：
Cohen, Dena E.;Supinski, Andrea M.;Guarente, Leonard P.
通讯作者：
Guarente, Leonard P.
影响因子：
8
作者：
Bauer, DE;Hatzivassiliou, G;Thompson, CB
通讯作者：
Thompson, CB
影响因子：
64.8
作者：
Barber, Matthew F.;Michishita-Kioi, Eriko;Xi, Yuanxin;Tasselli, Luisa;Kioi, Mitomu;Moqtaderi, Zarmik;Tennen, Ruth I.;Paredes, Silvana;Young, Nicolas L.;Chen, Kaifu;Struhl, Kevin;Garcia, Benjamin A.;Gozani, Or;Li, Wei;Chua, Katrin F.
通讯作者：
Chua, Katrin F.