Calorie Restriction and immune Response in Humans

人类的热量限制和免疫反应

• 批准号: 7404487
• 负责人: SIMIN Nikbin MEYDANI
• 金额: $ 15.72万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-15 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7404487
• 关键词: Adult; Adverse effects; Affect; Age; Aging; Animal Model; Animals; Antibodies; Antibody Formation; Biological; Biological Markers; Body Composition; Caloric Restriction; Cell physiology; Cells; Communicable Diseases; Defect; Delayed Hypersensitivity; Dinoprostone; Disease; Documentation; Elderly; Energy Intake; Enrollment; Event; Funding; Health; Human; Immune; Immune response; Immune system; Immunity; Immunologic Suppressor Factors; Immunologic Tests; In Vitro; Incidence; Inflammatory; Interferons; Interleukin-2; Interleukin-4; Interleukin-6; Intervention; Letters; Long-Term Effects; Longevity; Malignant Neoplasms; Measurement; Measures; Mediating; Mediator of activation protein; Metabolism; Mitogens; Mixed Lymphocyte Culture Test; Molecular; Morbidity - disease rate; Multi-Institutional Clinical Trial; Mus; Outcome; Overweight; Parents; Pathology; Personal Satisfaction; Phase; Phase II Clinical Trials; Physiology; Production; Proliferating; Publications; Randomized Controlled Clinical Trials; Rattus; Reaction; Recovery; Regulation; Reporting; Research Personnel; Risk Factors; Signal Transduction; Skin; Splenocyte; T memory cell; T-Cell Proliferation; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Vaccines; Woman; age related; clinically relevant; cytokine; cytotoxicity; extracellular; human TNF protein; immune function; improved; in vivo; insight; macrophage; men; mortality; neoplastic; programs; response; tumor

DESCRIPTION (provided by applicant): Aging is associated with impaired regulation of the immune system, which contributes to the increased incidence of infectious, inflammatory and neoplastic diseases observed in elderly subjects as well as their prolonged post-illness recovery periods. In addition, these changes were shown to be predictive of morbidity and mortality in animal models and humans. While all cells of the immune system contribute to the impaired immunity of old age, T cells are the main contributors, with age related changes reported in both in vivo and in vitro measures of T cell function across all species including humans. Calorie restriction (CR) has been shown to affect many age sensitive immunological responses in animal models, but information related to the effects of CR on immune response of humans is lacking. Preliminary results from the pilot phase of the two-step NIA-supported multi-center clinical trial to determine the biological effects of CR in humans [Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 1], showed that CR significantly improved delayed type hypersensitivity skin response, as well as T cell proliferation, in humans while decreasing production of T cell suppressive factor, PGE2. Thus, we hypothesize that long term CR intervention in adult subjects will enhance the immune response, as indicated by improved T cell-mediated function and reduced production of inflammatory mediators. Furthermore, we hypothesize that these CR-mediated effects on T cells are due to decrease in PGE2 production and/ or intrinsic changes in T cells. We propose to test this hypothesis utilizing subjects enrolled in the second phase of the NIA supported multi-center randomized controlled clinical trial, CALERIE Phase 2. The overall aim of CALERIE Phase 2 is to test the effects of 2 year, 25% CR from baseline energy intake, in adult subjects, on physiology, metabolism, body composition, risk factors for age-related pathologies, and its potential adverse effects. The specific aims of this project are to determine the effect of 2 y, 25% CR on T cell-mediated functions of adult subjects, as well as to explore its underlying mechanisms. Specifically the effect of CR on immune cell profile, proliferate ability of specific T cell subsets, intracellular and extracellular IL-2, IFNy, as well as PGE2 production, will be evaluated before, and following 1 and 2 years of 25% CR. The results from this study will be the first documentation of the impact of CR on immune response in humans, a biologically meaningful and clinically relevant marker shown to be sensitive to CR in various animal models. The proposed studies will also explore the underlying mechanisms of CR-induced modulation of the immune response and will add valuable information to the parent CALERIE Phase 2 studies by providing insight into the cellular and molecular mechanisms of CR induced health effects.

描述（由申请人提供）：衰老与免疫系统的调节受损有关，这有助于增加在老年受试者中观察到的感染性，炎症性和肿瘤性疾病的发病率以及其延长的后胸膜后恢复期。此外，这些变化被证明可以预测动物模型和人类的发病率和死亡率。尽管免疫系统的所有细胞都会导致老年免疫力受损，但T细胞是主要因素，在包括人类在内的所有物种中，体内和体外T细胞功能的体外测量均报告了与年龄相关的变化。卡路里限制（CR）已被证明会影响动物模型中的许多年龄敏感免疫反应，但是缺乏与CR对人类免疫反应的影响有关的信息。 Preliminary results from the pilot phase of the two-step NIA-supported multi-center clinical trial to determine the biological effects of CR in humans [Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE) Phase 1], showed that CR significantly improved delayed type hypersensitivity skin response, as well as T cell proliferation, in humans while decreasing production of T cell suppressive factor, PGE2.因此，我们假设成人受试者的长期CR干预将增强免疫反应，如T细胞介导的功能改善和炎症介质的产生减少所表明。此外，我们假设这些CR介导的对T细胞的影响是由于PGE2产生的降低和/或T细胞内固有变化所致。我们建议在NIA支持的多中心随机对照临床试验，Calerie阶段2的第二阶段中使用受试者进行检验，Calerie阶段2。卡尔里（Calerie）第2阶段的总体目的是测试2年的25％CR的影响，基线能量摄入量为25％，基线能量摄入，在成人，代谢，体外疾病，风险及时及其风险及时及其及时的病因，并及时及其及时的病毒效果，并及时及其及时的病理。该项目的具体目的是确定2 y，25％Cr对成人受试者T细胞介导的功能的影响，以及探索其基本机制。具体来说，将在1和2年的25％Cr之前评估CR对特定T细胞亚群的增殖能力，特定T细胞子集的增殖能力，细胞内和细胞外IL-2以及PGE2产生的影响。这项研究的结果将是CR对人类免疫反应的影响的第一个文献，该影响是一种生物学上有意义且与临床相关的标志物，在各种动物模型中对CR敏感。拟议的研究还将探索CR诱导的免疫反应调节的潜在机制，并通过深入了解CR诱导的健康效应的细胞和分子机制，从而为父级Calerie 2阶段研究添加宝贵的信息。