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

项目摘要。 本行政补编申请是根据PA-20-227-行政部门提出的 膳食补充剂研究补充剂(不允许服用补充剂临床试验)。 使用褪黑素作为膳食补充剂来支持睡眠和降低癌症风险的情况正在迅速增长。 褪黑激素作为昼夜节律的荷尔蒙标志物被广泛研究，然而，它的功能与 关于饮食或饮食模式的研究很少。褪黑素的合成、代谢和作用方式是 与线粒体功能紧密相连。因此，影响线粒体功能的生活方式极有可能 调节褪黑激素的产生、降解和活性。限时喂养/进食(TRF/Tre)是一种 饮食干预，将每日卡路里摄入量限制在6-12小时的一致窗口内。动物体内的TRF 系统地影响多个器官和大脑区域的线粒体功能。人类参与者正在经历 TrE干预也显示了肌肉线粒体功能的改善。这些初步观察结果 提出饮食模式可以调节褪黑激素功能的假设。 此补充资金申请将利用最近结束的随机对照试验，时间为10小时 轮班工人中的Tre。在基线和干预后收集的血浆将被用来测试TRE 影响血浆褪黑激素及其代谢物的水平。接下来，血浆过继转移实验将 定量评估Tre单独或联合补充褪黑素对血浆的影响 线粒体在正常细胞和癌细胞中起作用。这些目标的成功实现将是第一次， 演示TRE是否影响血浆褪黑激素水平，以及TRE和褪黑激素如何相互作用来影响 线粒体在正常细胞和癌症细胞中发挥作用。

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.