Circadian Clock and Dietary Restriction

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Diet is an important factor influencing health and disease. Calorie restriction (CR) improves metabolism, delays aging, and reduces the incidence of many age-associated diseases such as cancer, diabetes, and cardiometabolic. mTOR signaling pathway plays a central role in the control of aging and CR mechanisms. We will expand the current model on the regulation of mTOR signaling by diet in vivo, by exploring crosstalk between diet and circadian rhythms in metabolic signaling and gene expression. We will test the hypothesis that CR reprograms the expression of mTOR regulatory network through circadian clock-dependent mechanisms. The reprogramming changes the balance in the mTOR network and impacts the response of mTOR signaling to growth factors and nutrients challenges. Reprogramming of circadian rhythms in mTOR signaling is important for metabolic adaptation to CR. In vivo and ex vivo approaches and wild-type and circadian clock mutant mice will be used to compare the impact of CR with the impact of AL and fasting on mTOR signaling. The study will help to dissect contributions of fasting and reduced calorie intake to CR improved metabolism and longevity.