Effects of Calorie Restriction and Mimetics on Protein Translation Rates In Vivo by a Novel Tandem Mass Spectrometric Method

Summer 2016

Chase Garcia : Nutritional Science - Physiology and Metabolism

Rose Hills Independent
Mentor: Marc Hellerstein

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.

I would like to thank the Rose Hills Foundation for their generous support of my project. This project will help me understand and appreciate what true research is and this will help me with my future graduate school aspirations and endeavors. I plan on applying to dual DVM (Doctorate of Veterinary Medicine)/PhD programs and this experience will help me get that much closer to realizing my goal. Without your financial help I don't think I would have been able to take this wonderful opportunity and would lack this experience which will be invaluable to my professional growth, so thank you.