Impact of Time-Restricted Feeding in Reducing Cancer Risk Through Optimizing Mitochondria Function

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Project Summary. This request for an administrative supplement is submitted in response to PA-20-227 - Administrative Supplements for Research on Dietary Supplements (Admin Supp Clinical Trial Not Allowed]. The use of melatonin as a dietary supplement to support sleep and reduce cancer risk is rapidly growing. Melatonin is extensively studied as a hormonal marker of the circadian rhythm, however, its function in relation of diet or dietary patterns is rarely studied. The synthesis, metabolism, and mode of action of melatonin are tightly linked to mitochondria function. Hence, lifestyles influencing mitochondria function are highly likely to modulate melatonin production, degradation, and activity. Time-restricted feeding/eating (TRF/TRE) is a dietary intervention that limits daily calorie intake to a consistent window of 6-12 hours. TRF in animals systemically affect mitochondria function in multiple organs and brain regions. Human participants undergoing TRE intervention also show improvement in muscle mitochondria function. These preliminary observations raise the hypothesis that eating patterns can modulate melatonin function. This supplemental funding request will leverage the recently concluded randomized controlled trial on 10 h TRE among shift workers. Plasma collected at baseline and post-intervention will be used to test whether TRE affects the plasma levels of melatonin and its metabolites. Next, plasma adoptive transfer experiments will quantitatively assess the impact of plasma from TRE alone or in combination with supplemental melatonin on mitochondria function in normal and cancer cells. Successful completion of these aims will, for the first time, demonstrate whether TRE affects plasma melatonin levels and how TRE and melatonin interact to influence mitochondria function in normal cells and in cancer.