Nsun5 in ribosome function and mammalian healthy lifespan

We found previously that lack of the Nsun5 gene leads to increased lifespan and stress resistance of yeast, worms and flies. However, if Nsun5 or any other similar enzyme that is able to modify ribosomal RNA is capable of modulating healthy lifespan of mammals is not known. Thus, the aims of this project encompass the measurement of the lifespan of mice of both sexes, in which Nsun5 is depleted in the whole-body. We will further evaluate if Nsun5 improves health and ameliorates frailty at advanced age of animals. Finally, we will investigate if and how loss of Nsun5 impacts on general and specific protein synthesis. Due to the high evolutionary conservation of Nsun5, we are convinced that conclusions obtained within this project are also applicable to humans. Thus, the experiments proposed here will contribute to a better understanding of the contribution of ribosomal RNA methylation to organismal fitness and probably pave the ground for the design of healthspan-extending strategies in humans.