Caloric restrictions and immune senescence

热量限制和免疫衰老

• 批准号: 6552298
• 负责人: JANKO Z. NIKOLICH
• 金额: $ 38.43万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6552298
• 关键词: Macaca mulatta; T cell receptor; T lymphocyte; age difference; aging; animal old age; caloric dietary content; cell mediated lymphocytolysis test; cell population study; cellular immunity; cooperative study; cytokine; cytotoxic T lymphocyte; cytotoxicity; dietary restriction; flow cytometry; gene expression; helper T lymphocyte; immunosenescence; lymphocyte proliferation; mature animal; microarray technology; nutrition related tag; thymus

DESCRIPTION (provided by applicant): Immune senescence is a state of diminished immune competence manifested by reduced ability to respond to and clear pathogens and tumors, and it is believed to significantly contribute to morbidity and mortality in older individuals. Caloric restriction (CR) is the only intervention that consistently and significantly prolongs lifespan and delays the age-associated morbidity and mortality in experimental animals, but its mechanism of action is incompletely understood. CR appears to exert beneficial effects on the aging rodent immune system. However, it is not known whether CR can reverse immune senescence, or whether CR would similarly impact the immune system of primates. In this proposal, we shall elucidate the effects of aging upon the immune system of Rhesus Macaques, and test the hypothesis that CR acts to maintain T-cell subset balance and preserve T-cell responsiveness in aged Rhesus Macaques. To that ene, we shall measure key immunological parameters known to be affected by aging in other species. Cross-sectional studies will be performed in young and old animals fed regular or CR diets. Specific aims will examine the effects of aging and CR on T-cell subset frequencies and function (Aim 1), thymic output and peripheral T-cell homeostasis (Aim 2), TCR diversity of T-cell subsets (Aim 3), and T-cell subset gene expression patterns (Aim 4). These studies will comprehensively and precisely characterize the effects of aging and CR in a real-life, outbred primate model. This will not only test the validity of observations in rodents, but also put limits on current hypotheses and allow for the rational setting of new ones.

描述（由申请人提供）：免疫衰老是一种免疫能力降低的状态，其反应能力降低并清除病原体和肿瘤，并且据信这显着有助于老年人的发病率和死亡率。热量限制（CR）是唯一一致且显着延长寿命并延迟实验动物中与年龄相关的发病率和死亡率的干预措施，但其作用机理却不完全理解。 CR似乎对衰老的啮齿动物免疫系统产生有益的影响。但是，尚不知道CR是否可以逆转免疫衰老，或者CR是否会类似地影响灵长类动物的免疫系统。 在此提案中，我们将阐明衰老对猕猴免疫系统的影响，并检验CR的假设，即CR可以保持T细胞子集平衡并保留老年恒河猕猴的T细胞反应性。为此，我们将测量已知会受到其他物种衰老影响的关键免疫学参数。将在喂养常规或CR饮食的年轻和老动物中进行横断面研究。具体目的将检查衰老和CR对T细胞子集频率和功能的影响（AIM 1），胸腺输出和周围T细胞稳态（AIM 2），T-Cell子集的TCR多样性（AIM 3）和T - 细胞子集基因表达模式（AIM 4）。 这些研究将全面，精确地表征在现实生活中的灵长类动物模型中衰老和CR的影响。这不仅将测试啮齿动物中观察结果的有效性，而且还限制了当前的假设，并允许新的假设的合理设置。