Abstract by Richard Carson
Chemistry and Biochemistry
Calorie Restriction Conditions May Modulate Aging Rates by Altering Ribosomal Maintenance and Quality
Calorie restriction (CR) is the gold standard intervention for increasing lifespan and healthspan in laboratory animals; decades of study suggest that these benefits result from an overall improvement in protein quality and maintenance. However, the biochemical mechanisms remain incompletely understood. Using a mouse model on CR, we performed kinetic and quantitative proteomics as well as RNA-sequencing to investigate nodes of proteome control. Our data show that a general slowdown of protein turnover results from CR. Additionally, the metabolic flux of ribosomal proteins shifts, suggesting significant changes in translational quality and ribosome maintenance. Further, this slowdown in protein translation may be accomplished by differential regulation of the peripheral cellular protein translational machinery. Overall, these changes are predicted to improve ribosome quality, increase translational fidelity, and increase time for proper co-translational protein folding. Our data provides evidence for a model in which the phenotypic benefits of CR arise from the cell actively perturbing translational controls to slow down proteome turnover.