Calorie restriction is one of the best-studied methods for extending longevity in laboratory animals, but the mechanism remains incompletely understood. Our lab combined RNA-Seq, RNA kinetics, quantitative proteomics, and kinetic proteomics in a novel unbiased application to calorie-restricted mouse tissue samples. An overall slowing of protein synthesis was observed, with evidence suggesting that alterations in tRNA metabolism are responsible: aminoacyl tRNA synthetase metabolism was found to differ significantly between calorie restriction and ad libitum diets, indicating changes in the available tRNA pool for protein synthesis. We hypothesize that decreasing the pool of charged tRNA available for translation allows the cell to lower both its energy consumption and protein synthetic burden, leading to the improvements in cellular and organismal health observed under calorie restriction.