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

项目摘要。 本行政补充申请是针对PA-20-227 -行政申请提交的。 膳食补充剂研究补充剂（不允许进行管理补充剂临床试验）。 使用褪黑激素作为膳食补充剂来支持睡眠和降低癌症风险正在迅速增长。 褪黑激素作为昼夜节律的激素标志物被广泛研究，然而，它在昼夜节律中的功能， 饮食或饮食模式的研究很少。褪黑激素的合成、代谢和作用方式 与线粒体功能紧密相连。因此，影响线粒体功能的生活方式很有可能 调节褪黑激素的产生、降解和活性。限制进食时间（TRF/TRE） 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TRF 全身性影响多个器官和脑区域中线粒体功能。人类参与者 TRE干预也显示肌肉线粒体功能的改善。这些初步意见 提出了饮食模式可以调节褪黑激素功能的假设。 这项补充资金申请将利用最近结束的10小时随机对照试验， 在轮班工作者中。基线和干预后采集的血浆将用于检测TRE是否 影响褪黑激素及其代谢物的血浆水平。接下来，血浆过继转移实验将 定量评估来自单独的TRE或与补充褪黑激素组合的血浆对 线粒体在正常细胞和癌细胞中起作用。成功地完成这些目标将首次， 证明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影响 线粒体在正常细胞和癌症中起作用。

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.