Effect of Calorie Restriction on Infection During Aging

描述(由申请人提供)：卡路里 限制(30%-40%)可延长啮齿动物的寿命。延长使用寿命 跨度是伴随着防止体重增加，保持 细胞介导的免疫功能，并降低恶性肿瘤和 肾脏疾病。尽管最近的研究表明，CR会改变 各种基因的表达，特别是那些与大分子有关的基因 损害，目前尚不清楚动物是否能够终身喂养CR饮食 成功地抵御了细菌感染。我们最近的研究表明， 饲喂铬的幼年C57BL/6小鼠更容易受到细菌感染 喂铝的小鼠。感染易感性的差异可能是由于 小鼠品系、能量摄取、维生素和补充量的差异 矿物质或体液免疫成熟延迟。因此，我们建议 比较2个品系小鼠CR研究的3种不同常用饮食 (C57LBL/6和Balb/C)对Th-1和Th-2细胞因子应答的差异 表情。我们将比较AIN-93饮食中加和不加的情况 维生素补充剂，2)减少碳水化合物的AIN-93CR饮食，但 增加蛋白质、脂肪和维生素，以等同于AL饮食；3)NIH-31，以及 用于CR研究的未定义但常用的啮齿动物食物。我们将衡量 盲肠结扎和盲肠结扎致多菌败血症的病死率 穿刺法(CLP)和幼年和老年小鼠的沙门氏菌病。要建立 青年(8mo)和老年人(24mo)对感染的易感性和抵抗力 ，我们将对巨噬细胞、Th-1和 Th-2细胞因子的产生及Th-1/Th-2和Th-2的cDNA超阵列分析 炎症反应细胞因子基因。这些研究将确定 CR在发展最佳免疫功能方面的作用，以抵御由 衰老过程中常见的细菌病原体。这一新信息可能会变得非常 有助于防止CR研究和/或期间突然发生感染 通过饮食或药物在人体内减肥的研究。

DESCRIPTION (provided by applicant): It is well established that calorie restriction (3O-4O percent) prolongs the life span in rodents. Increased life span is accompanied by preventing the increase in body weight, maintaining cell-mediated immune function, and decreasing the incidence of malignancies and renal diseases. Although recent studies have revealed that CR alters the expression of various genes, particularly those involved in macromolecular damage, it remains unknown whether animals fed a lifelong CR diet are able to successfully ward off bacterial infection. Our recent studies showed that CR-fed young C57BL/6 mice are more susceptible to bacterial infection than AL-fed mice. The differences in susceptibility to infection could be due to differences in strains of mice, energy uptake, supplementation of vitamins and minerals or delayed maturity of humoral immunity. We, therefore, propose to compare 3 different commonly used diets for CR studies in 2 strains of mice (C57LBL/6 and Balb/C) which differ in their response to Th-1 and Th-2 cytokine expression. We will compare 1) the AIN-93 diet with and without additional vitamin supplements, 2) the AIN-93 CR diet with reduced carbohydrates but increased protein, fat and vitamins to equal the AL diet, and 3) NIH-3 1, an undefined but commonly used rodent chow diet for CR studies. We will measure the mortality rate from polymicrobial sepsis induced by cecal ligation and puncture (CLP) and from salmonellosis in young and old mice. To establish the susceptibility and resistance to infection both in young (8 mo) and old (24 mo) mice, we will carry out detailed functional studies of macrophages, Th-1 and Th-2 cytokine production, and cDNA superarray analysis for Th-1/Th-2 and inflammatory response cytokine genes. These studies will establish the role of CR in developing optimal immune function to ward off infection arising from common bacterial pathogens during aging. This new information may become very useful to prevent any sudden onset of infection during CR studies and/or studies of weight reduction either by diet or by drugs in humans.