Chase Garcia Rose Hills
Effects of Calorie Restriction and Mimetics on Protein Translation Rates In Vivo by a Novel Tandem Mass Spectrometric Method
Caloric restriction (CR), defined as under-nutrition without malnutrition, has been shown in a variety of organisms to increase maximal lifespan upwards of 70%. CR also been shown to have other health benefits not limited to reduced carcinogenesis, increased insulin sensitivity, and reduced cardiovascular disease risk. There are several theories as to how this works, but we still lack a fundamental, mechanistic understand of this phenomenon. Based on research that suggests hepatic proteome replacement rates may be a critical, predictive link between caloric restriction and increased life expectancy, I hypothesize that CR and CR mimetics will decrease global protein translation rates and that this can be measured in vivo by use of a novel tandem mass spectrometric method developed in the Hellerstein lab. This finding would have several potentially important implications: first, that the global rate of message translation is a modulatory process in mammalian tissues; second, that protein translation rate per se may have an impact on health and cellular homeostasis; and third, that reduced protein translation rates may serve as an in vivo biomarker for the benefits of CR. Expanding our mechanistic understanding of CR can advance our knowledge on aging and age-related diseases and the potential applications are numerous. Being able to reduce CR to its core biochemical components might allow for more effective preventative and personalized treatment for patients suffering from some of the biggest diseases killing Americans today.