Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.
Autophagy mediates pharmacological lifespan extension by spermidine and resveratrol.
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DOI：
10.18632/aging.100110
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发表时间：
2009-12-23
期刊：
影响因子：
--
通讯作者：
Kroemer G
中科院分区：
文献类型：
--
作者：
Morselli E;Galluzzi L;Kepp O;Criollo A;Maiuri MC;Tavernarakis N;Madeo F;Kroemer G
虽然自噬被广泛认为是一种导致细胞死亡的自毁机制，但越来越多的证据表明自噬通常介导细胞保护，从而避免应激细胞的凋亡或坏死死亡。我们小组最近的证据表明，自噬也参与了延长寿命的药理学操作。外源性多胺亚精胺可以延长酵母、线虫和苍蝇的寿命（同时诱导自噬）。同样，白藜芦醇可以触发不同生物体细胞的自噬，延长线虫的寿命，并改善经历代谢应激的人类细胞的适应性。当必需的自噬调节剂在遗传上失活或失活时，这些有益的作用丧失，表明自噬是亚精胺和白藜芦醇的细胞保护和/或抗衰老作用所必需的。遗传和功能研究表明，亚精胺抑制组蛋白乙酰化酶，而白藜芦醇激活组蛋白去乙酰化酶Sirtuin 1赋予细胞保护/长寿。虽然它仍然难以捉摸是否相同的组蛋白（或其他细胞核或细胞质蛋白）作为亚精胺和白藜芦醇的下游目标，这些结果指出蛋白质低乙酰化在自噬控制和调节寿命的重要作用。
Although autophagy has widely been conceived as a self-destructive mechanism that causes cell death, accumulating evidence suggests that autophagy usually mediates cytoprotection, thereby avoiding the apoptotic or necrotic demise of stressed cells. Recent evidence produced by our groups demonstrates that autophagy is also involved in pharmacological manipulations that increase longevity. Exogenous supply of the polyamine spermidine can prolong the lifespan of (while inducing autophagy in) yeast, nematodes and flies. Similarly, resveratrol can trigger autophagy in cells from different organisms, extend lifespan in nematodes, and ameliorate the fitness of human cells undergoing metabolic stress. These beneficial effects are lost when essential autophagy modulators are genetically or pharmacologically inactivated, indicating that autophagy is required for the cytoprotective and/or anti-aging effects of spermidine and resveratrol. Genetic and functional studies indicate that spermidine inhibits histone acetylases, while resveratrol activates the histone deacetylase Sirtuin 1 to confer cytoprotection/longevity. Although it remains elusive whether the same histones (or perhaps other nuclear or cytoplasmic proteins) act as the downstream targets of spermidine and resveratrol, these results point to an essential role of protein hypoacetylation in autophagy control and in the regulation of longevity.
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DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
影响因子：
12.4
作者：
Criollo, A.;Maiuri, M. C.;Kroemer, G.
通讯作者：
Kroemer, G.
影响因子：
4.3
作者：
Demidenko, Zoya N.;Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.
影响因子：
4.3
作者：
Demidenko, Zoya N.;Zubova, Svetlana G.;Blagosklonny, Mikhail V.
通讯作者：
Blagosklonny, Mikhail V.