Fok Wilson C, Bokov Alex, Gelfond Jonathan, Yu Zhen, Zhang Yiqiang, Doderer Mark, Chen Yidong, Javors Martin, Wood William H, Zhang Yongqing, Becker Kevin G, Richardson Arlan, Pérez Viviana I
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
Aging Cell. 2014 Apr;13(2):311-9. doi: 10.1111/acel.12175. Epub 2013 Dec 5.
Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone.
雷帕霉素（Rapa）和饮食限制（DR）一直被证明能延长寿命。为了研究Rapa和DR是否影响小鼠体内的相似通路，我们比较了随意进食（AL）、Rapa、DR或Rapa与DR联合使用（Rapa + DR）对小鼠肝脏转录组和代谢组的影响。主成分分析表明，Rapa和DR属于不同的组。与AL喂养的小鼠相比，Rapa或DR处理后有超过2500个基因发生了显著变化；其中超过80%的基因是DR或Rapa所特有的。当将基因分组到通路中时也有类似的发现；三分之二的通路是由DR或Rapa单独独特改变的。代谢组显示Rapa和DR之间的差异更大；Rapa处理的小鼠中没有代谢物与AL小鼠有显著变化，而DR小鼠中有173种代谢物发生了变化。有趣的是，与AL相比，Rapa + DR显著改变的基因数量是单独DR或Rapa显著改变基因数量的两倍。总之，DR或Rapa对肝脏的整体影响有很大不同，Rapa和DR联合使用会导致大量基因和代谢物发生改变，而单独任何一种处理都不会使其发生显著变化，这表明DR和Rapa联合使用在延长寿命方面比单独任何一种处理都更有效。
