Ageing and non-coding RNA: does the thirst for ribosomes control lifespan?

衰老在真核生物中几乎是普遍存在的，在简单易处理的生物体中，解剖调节衰老的途径将为人类衰老的驱动因素提供线索。虽然衰老似乎是不可避免的，但遗传研究揭示了强烈影响衰老速度的途径。事实上，这些途径中的许多都集中在一个高度保守的过程：核糖体合成。细胞需要大量的核糖体来满足蛋白质合成的要求，并投入大量的资源来合成核糖体。为了满足这一需求，基因组包含数百个编码核糖体（rRNA）的基因拷贝，这些基因以称为核糖体DNA（rDNA）的串联阵列组织。rDNA的拷贝数是可变的，我们最近已经表明，一个关键的途径，调节酵母中的老化也控制rRNA基因的扩增，以响应环境。这提出了一个令人兴奋的想法，即衰老可能是由细胞对核糖体合成的需求驱动的，核糖体合成是一个高度保守但可控的过程。令人惊讶的是，核糖体合成和rDNA拷贝数对衰老的影响在多细胞生物中几乎完全没有研究。我们认为，个体差异性对于理解衰老至关重要，而rDNA拷贝数在个体之间差异很大。因此，本项目的目的是阐明核糖体合成如何影响个体蠕虫的衰老。由于蠕虫的自然寿命短和实验易处理性，它们是研究衰老的极好模式生物。该项目将扩展到博士学位，旨在了解衰老和抗应激能力如何受到核糖体合成的大量但可变的资源消耗的影响。

Ageing is almost universal in eukaryotes and dissecting pathways that modulate ageing in simple tractable organisms will provide clues to the drivers of human ageing. Although ageing appears inevitable, genetic studies have revealed pathways that strongly influence the rate of ageing. In fact, many of these pathways converge on a highly conserved process: ribosome synthesis. Cells need a huge amount of ribosomes to meet protein synthesis requirements and devote vast resources to synthesising ribosomes. To meet this demand, genomes contain hundreds of copies of the genes encoding ribosomal (rRNA), organised in tandem arrays called ribosomal DNA (rDNA). The number of rDNA copies is variable, and we have recently shown that a key pathway which modulates ageing in yeast also controls amplification of rRNA genes in response to the environment. This raises the exciting idea that ageing may be driven by the cellular demand for ribosome synthesis, a highly conserved but controllable process. Surprisingly, the effects of ribosome synthesis and rDNA copy number on ageing are almost completely unstudied in multicellular organisms. We think that individual variability is crucial to understanding ageing and rDNA copy number varies dramatically between individuals. Therefore, the aim of this project is to elucidate how ribosome synthesis influences ageing in individual worms. Worms are an excellent model organism for ageing due to their short natural lifespan and experimental tractability. This project would extend into a PhD aimed at understanding how ageing and stress resistance are impacted by the massive but variable resource consumption of ribosome synthesis.