Biomarkers of Caloric Restriction in Humans: the CALERIE Biorepository

 描述（由申请人提供）：衰老是一个复杂的生物学过程，涉及身体的所有组织及其通过代谢和遗传生物学的相互作用。一段时间以来，人们已经知道，减少热量摄入可以促进从酵母到昆虫、蠕虫、啮齿动物和非人类灵长类的广泛真核生物的中值和最大寿命的延长。已经有许多关于热量限制对持续长达六个月的衰老替代生物标志物的影响的对照和非对照研究，但在CALERIE研究开始之前，长期热量限制的影响一直没有出现。CALERIE研究旨在通过一项随机对照试验，评估在不强制改变饮食组成的情况下，对人类受试者进行两年持续且显著的热量限制的效果。干预的持续时间和治疗分配的随机化性质以前从未在人体研究中尝试过。这些因素，结合研究的实质性规模，在生理评估中对细节的仔细关注，仔细收集广泛的临床数据，以及从研究参与者中收集的样本的广泛生物储存库，使生物储存库成为研究人类受试者中期热量限制的系统分子生物学效应的宝贵资源。有了这个奖项，我们将在五年内支持以下项目：维护杜克大学的数据存储库，维护佛蒙特大学的生物储存库，将临床数据与生物样本联系起来的能力，以及管理样本使用的CALERIE调查员委员会。该储存库将为目前和未来研究人类热量限制的研究人员提供收集的数据和样本。此外，我们将进行初步的 使用生物储存库样本对热量限制的影响进行系统的生物学研究。具体目标是：1）维护CALERIE数据库和生物样本库; 2）管理CALERIE样本库的应用程序; 3）解决有关人类卡路里限制生物学的次要问题。当前CALERIE数据; 4）利用分子研究来管理CALERIE数据库，以促进系统生物学方法来理解人类的卡路里限制。在这个资助期结束时，我们将拥有一个丰富的生物和临床数据库，可供科学界调查关于热量限制对人类衰老生物学作用的无数假设。

 DESCRIPTION (provided by applicant): Aging is a complex biological process, involving all tissues of the body and their interactions through metabolism and genetic biology. It has been known for some time that reducing caloric intake can promote extension of median and maximal lifespan across a broad range of eukaryotic organisms from yeast, through insects, worms, rodents and nonhuman primates. There have been numerous controlled and uncontrolled studies of the effects of caloric restriction on surrogate biomarkers of aging lasting up to six months, but the effects of longer term calorie restriction notably have been absent until the inception of the CALERIE study. The CALERIE study was designed to assess the effects of two years of sustained and significant caloric restriction without enforced changes of dietary composition in human subjects in a randomized controlled trial. The duration of the intervention and the randomized nature of the treatment assignment had never previously been attempted in a human study. These factors, combined with the substantial size of the study, the careful attention to detail in the physiologic assessments, careful collection of extensive clinical data, and the extensive biorepository of samples collected from study participants, make the biorepository an invaluable resource for the investigation of the systematic molecular biological effects of medium term caloric restriction in human subjects. With this award, we will support the following projects for five years: maintenance of the data repository at Duke University, maintenance of the biorepository at the University of Vermont, the ability to link clinical data wih biological samples, and the committee of CALERIE investigators who steward use of the samples. This repository will provide access to collected data and samples to present and future investigators investigating caloric restriction in humans. In addition, we will conduct preliminary systems biological investigations of the effects of caloric restriction using the biorepository samples. The Specific Aims are: 1) Maintenance of the CALERIE Data Repository and Biological Sample Repository; 2) Stewardship of applications for use of the CALERIE Sample Repository; 3) Address secondary questions regarding the biology of calorie restriction in humans. of current CALERIE data; 4) Curation of the CALERIE Database with molecular studies to promote a systems biology approach to the understanding of calorie restriction in humans. At the end of this funding period we will have available a rich biological and clinical data repository available to the scientific community for the investigation of innumerable hypotheses about the role of calorie restriction on the human aging biology.