Circadian Clock and Dietary Restriction

昼夜节律时钟和饮食限制

• 批准号: 10579704
• 负责人: Roman V Kondratov
• 金额: $ 47.17万
• 依托单位: CLEVELAND STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579704
• 关键词: ARNTL gene; Acute; Address; Affect; Age; Aging; Amino Acids; Animals; Behavior; Behavioral; Blood; Caloric Restriction; Calories; Circadian Rhythms; Complex; Data; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Energy Intake; Equilibrium; FRAP1 gene; Fasting; Food; Gene Expression; Genes; Glucose; Growth Factor; Health; Hour; Incidence; Insulin; Intake; Longevity; Malignant Neoplasms; Mammals; Metabolic; Metabolism; Modeling; Molecular; Mus; Mutant Strains Mice; Nutrient; Organism; Pathway interactions; Periodicity; Phosphotransferases; Physiological; Physiology; Play; Prevention; Publishing; Regulation; Role; Signal Transduction; System; TSC1 gene; TSC1/2 gene; Testing; Time; Tissues; cardiometabolism; circadian; circadian pacemaker; detection of nutrient; dietary restriction; experimental study; extracellular; feeding; improved; in vivo; mTOR Signaling Pathway; prevent; public health relevance; response; transcriptional reprogramming; treatment strategy

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.

饮食是影响健康和疾病的重要因素。热量限制（CR）改善新陈代谢， 延缓衰老，降低许多与年龄相关的疾病的发病率，如癌症，糖尿病， 心脏代谢的mTOR信号通路在衰老和CR机制的控制中起着核心作用。我们 将通过探索串扰，扩展目前关于饮食在体内调节mTOR信号传导的模型。 饮食和代谢信号和基因表达的昼夜节律之间的联系。我们将检验这个假设 CR通过生物钟依赖性调节mTOR调节网络的表达， 机制等重编程改变了mTOR网络中的平衡，并影响了细胞对细胞因子的反应。 mTOR信号传导对生长因子和营养素的挑战。mTOR中昼夜节律的重编程 信号传导对于代谢适应CR是重要的。体内和离体方法以及野生型和 昼夜节律钟突变小鼠将用于比较CR的影响与AL和禁食对 mTOR信号传导。这项研究将有助于剖析禁食和减少卡路里摄入对CR的贡献 改善新陈代谢和延长寿命。