Abstract by Joshua McPhie
Chemistry and Biochemistry
Phosphoproteomic Investigation of the Mechanism of Calorie Restriction Attenuation by Dietary Protein Signaling
Calorie restriction has been shown to significantly increase lifespan and prevent age-related diseases. However, when dietary protein is also increased, the benefits of calorie restriction are largely reduced to baseline health. Even though calorie restriction has been studied for decades, the mechanisms behind it remain unknown. We hope to shed some light on this subject by analyzing the activity of the master kinase mTOR. mTOR is a nutrient sensor, capable of recognizing both cell stress caused by lack of caloric intake as well as dietary protein. We hypothesize that dietary protein intake and induced cell stress (via calorie restriction) will have opposite effects on mTOR. We propose that these effects on mTOR cause the decrease in calorie restriction benefits under high dietary protein conditions. We inferred the relative activity of mTOR under low and high dietary protein conditions by comparing the concentrations of modified mTOR substrates. The two methods we used for this comparison were western blotting and phosphoproteomics.