A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
A Systems Approach to Reverse Engineer Lifespan Extension by Dietary Restriction.
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一种通过饮食限制逆转工程师寿命延长的系统方法
DOI：
10.1016/j.cmet.2016.02.002
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发表时间：
2016-03-08
期刊：
影响因子：
29
通讯作者：
Han JD
中科院分区：
文献类型：
--
作者：
Hou L;Wang D;Chen D;Liu Y;Zhang Y;Cheng H;Xu C;Sun N;McDermott J;Mair WB;Han JD
饮食限制（DR）是延长寿命的最有力的自然手段。虽然有几个基因可以介导对替代DR方案的反应，但没有一个单一的基因干预可以概括DR的全部效果，并且对于不同的DR方案也没有统一的系统。在这里，我们获得时间分辨的转录组在秀丽隐杆线虫的热量限制和间歇性禁食，并发现早期和晚期的反应涉及代谢和细胞周期/DNA损伤，分别。我们发现DR调节器的三个网络模块的目标特异性。通过对代表离散模块的节点进行遗传操作，我们诱导了随着多个节点的扰动而逐渐类似于DR的转录组。同时靶向所有三个节点会导致极长寿的动物对DR难治性。这些结果和动态模拟表明，调节器之间的广泛反馈控制可能会被利用来驱动调节电路到更年轻的稳定状态，重现DR的全部效果。
Dietary restriction (DR) is the most powerful natural means to extend lifespan. Although several genes can mediate responses to alternate DR regimens, no single genetic intervention has recapitulated the full effects of DR, and no unified system is known for different DR regimens. Here we obtain temporally resolved transcriptomes during calorie restriction and intermittent fasting in Caenorhabditis elegans, and find that early and late responses involve metabolism and cell cycle/DNA damage, respectively. We uncover three network modules of DR regulators by their target specificity. By genetic manipulations of nodes representing discrete modules, we induce transcriptomes that progressively resemble DR as multiple nodes are perturbed. Targeting all three nodes simultaneously results in extremely long-lived animals that are refractory to DR. These results and dynamic simulations demonstrate that extensive feedback controls among regulators may be leveraged to drive the regulatory circuitry to a younger steady state, recapitulating the full effect of DR.
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影响因子：
14.9
作者：
Contrino S;Smith RN;Butano D;Carr A;Hu F;Lyne R;Rutherford K;Kalderimis A;Sullivan J;Carbon S;Kephart ET;Lloyd P;Stinson EO;Washington NL;Perry MD;Ruzanov P;Zha Z;Lewis SE;Stein LD;Micklem G
通讯作者：
Micklem G
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
64.8
作者：
Honjoh, Sakiko;Yamamoto, Takuya;Nishida, Eisuke
通讯作者：
Nishida, Eisuke
影响因子：
64.5
作者：
Tepper RG;Ashraf J;Kaletsky R;Kleemann G;Murphy CT;Bussemaker HJ
通讯作者：
Bussemaker HJ
影响因子：
4.5
作者：
Sagi D;Kim SK
通讯作者：
Kim SK