The role of translational control in regulating chronological lifespan

试图理解为什么我们会变老是一个长期存在的问题。这是一个复杂的问题，因为影响我们衰老方式的不仅仅是我们的基因，还有环境和饮食。为了确定衰老过程的潜在机制，研究了简单的模式生物。萌芽酵母，酿酒酵母，为研究衰老提供了最简单和被广泛采用的模式生物之一。它提供了一种相对简单、遗传上易于处理的系统，并在我们对人类细胞衰老过程的理解方面取得了许多重大进展。例如，它已被用于识别主要的促衰老途径，这些途径在从酵母到人类的各种有机体中高度保守。我们正在使用这个模型，并发现一个关键的蛋白质合成因素对确保长寿很重要。蛋白质合成因子是在每个细胞中合成所有新蛋白质所必需的，这个过程被称为“翻译”。这些“蛋白质合成因子”将编码基因序列的信使分子RNA翻译成蛋白质分子。每个细胞中有数以千计的RNA分子，每个分子携带一种不同蛋白质的指令(或编码)。蛋白质合成因子必须以正确的方式与每一种RNA相互作用，以便每一种新的蛋白质都以正确的比例正确地合成。通过改善我们对正常细胞中这种过程如何工作的基本理解，它可以帮助科学家理解这种过程发生变化的疾病。我们的初步数据表明，在我们的酵母衰老模型中，一个这样的翻译因子(EIF4G)对于长寿是必不可少的。该项目将解决eIF4G如何规范老化过程中的翻译，以及是否有特定的eIF4G目标RNA来确保正常健康的衰老过程。

Trying to understand why do we age has been a long standing question. It is a complicated question because it is not only our genes, but the environment and diet that affects the way we age. In order to identify mechanisms underlying the ageing processes, simple model organisms have been studied. The budding yeast, Saccharomyces cerevisiae, provides one of the simplest and widely adopted model organisms to study ageing. It provides a relatively simple, genetically tractable system, and has provided a number of significant advances in our understanding of the ageing process in human cells. For example, it has been used to identify major pro-ageing pathways which are highly conserved in organisms ranging from yeast to humans. We are using this model and have found that a that a key protein synthesis factor is important for ensuring longevity. Protein synthesis factors are required to synthesize all new proteins in each cell, a process referred to as "translation". These 'protein synthesis factors' translate RNA, a messenger molecule that encodes gene sequences, into protein molecules. There are many thousands of RNA molecules in each cell, each one carrying instructions (or coding) for a different protein. The protein synthesis factors must interact with each RNA in the right way so that each new protein is made correctly and in the correct proportions. By improving our fundamental understanding of how such processes work in normal cells it can help scientists understand diseases in which this process is altered. Our preliminary data indicate that one such translation factor (eIF4G) is essential for longevity in our yeast model of ageing. This project will address how eIF4G regulates translation during ageing and whether there are specific eIF4G target RNAs that ensure a normal healthy ageing process.