2012年8月16日 电 /生物谷BIOON/ --英国利物浦大学研究人员开发出一种新方法来鉴定参与饮食调节寿命延长的基因。利用这种方法，他们在酵母中找出3个新的延长寿命的基因。
利物浦大学研究人员和美国阿肯色大学研究人员合作研究饮食限制，即限制饮食中某些因子(比如热量)但是不会导致营养不良。已知饮食限制能够增加从酵母到猴子的寿命，并且在这之前，科学家们也已发现很多基因与饮食限制相关联。在当前这项研究中，研究人员开发出一种方法来研究基因彼此之间如何相互作用。这允许研究人员鉴定出调节饮食限制导致寿命延长的新基因。他们证实酵母中三个基因通过饮食限制相关的机制来延长寿命。
在这些鉴定出的新基因当中，一些基因可能在人类中也有类似功能，因而可能成为抗衰老介入治疗的潜在靶标。领导这项研究的 Joao Pedro de Magalhaes博士解释道，“一些正在进行临床测试的抑制人衰老的靶标最初就是在酵母中发现的，因此我们特别想继续这项研究以便最终能够解决人衰老过程和开发出治疗与年龄相关的疾病的方法。此外，我们的方法能够被用来预测哺乳动物和甚至人类中参与饮食限制调节寿命延长的基因。我们在酵母中测试了我们的预测，这是因为它能够更快开展和成本更低，但是我们如今正在寻求资金赞助以便在更加复杂的模式动物中测试这项研究。我对人们最终能够开发出抗衰老药物感到非常乐观。”(生物谷Bioon.com)
本文编译自Study pinpoints genes involved in diet-mediated life-extension
doi: 10.1371/journal.pgen.1002834
PMC:
PMID:
Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes
Daniel Wuttke1, Richard Connor2, Chintan Vora1, Thomas Craig1, Yang Li1, Shona Wood1, Olga Vasieva3, Robert Shmookler Reis4,5, Fusheng Tang2*, João Pedro de Magalhães
Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process.
