Effect of Calorie Restriction on Infection During Aging

描述（由申请人提供）：众所周知，卡路里 限制（30 - 40%）缩短啮齿动物的寿命。寿命增加 跨度是伴随着防止体重的增加，保持 细胞介导的免疫功能，并降低恶性肿瘤的发病率， 肾脏疾病虽然最近的研究表明，CR改变了 各种基因的表达，特别是那些参与大分子 尽管如此，仍然不清楚终身喂食CR饮食的动物是否能够 成功抵御细菌感染。我们最近的研究表明， CR喂养的年轻C57 BL/6小鼠比对照小鼠更容易受到细菌感染。 AL喂养的小鼠。感染易感性的差异可能是由于 小鼠品系、能量摄取、维生素补充和 矿物质或体液免疫成熟延迟。因此，我们建议 在2种小鼠品系中比较用于CR研究的3种不同常用饮食 （C57 LBL/6和Balb/C），它们对Th-1和Th-2细胞因子的反应不同 表情我们将比较1）AIN-93饮食与和没有额外的 维生素补充剂，2）AIN-93 CR饮食减少碳水化合物，但 增加蛋白质、脂肪和维生素以与AL饮食相等，和3）NIH-31， 未定义但常用于CR研究的啮齿动物饲料。我们将测量 盲肠结扎引起的多微生物败血症的死亡率， 穿刺（CLP）和沙门氏菌病在年轻和老年小鼠。建立 年轻（8个月）和老年（24个月）对感染的敏感性和抵抗力 小鼠，我们将进行详细的功能研究巨噬细胞，Th-1和 Th-2细胞因子的产生，以及Th-1/Th-2和Th-3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，以抵御感染引起的 衰老过程中常见的细菌病原体。这些新信息可能会变得非常 可用于预防CR研究期间的任何突发感染和/或 通过饮食或药物减轻人类体重的研究。

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.