For thousands of years fasting has been recommoned to prevent or treat a variety of diseases. More recent scientific studies have confirmed that various approaches that lead to a fasting state - caloric restriction, time-restricted feeding or intermittent fasting can have huge metabolic benefits that lead to reduced metabolic diseases and perhaps promote lifespan. In contrast, we know most people in today's society are almost always in a fed state and rarely are fasted. The question we want to know is how does fasting improve health? In other words, what pathways are turned on (or off) to mediate the metabolic benefits of fasting. We are currently using cell and mouse models as well as studies in humans to try to determine the benefits of various fasting modalities (caloric restriction, time restricted feeding, etc.) and the mechanisms through which they works. Additionally, the composition of the diet also is a major factor that contributes to health. Thus, we are also studying how modulating specific dietary components can modulate the effects of fasting.