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

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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.