Caloric Restriction and Aging in Humans

描述：（由申请人提供）初级老化是渐进的 随着年龄的增长，结构和功能的退化， 独立于疾病和生活方式/环境因素。放缓 初级老化导致最大寿命的增加。热量限制 (CR)减缓各种短命生物的初级衰老，如孔雀鱼， 苍蝇、老鼠和老鼠。目前尚不清楚CR是否会减缓人类的原发性衰老。 二次老化是由于疾病的过程和有害的 生活方式/环境因素。防止二次老化导致 不延长最大寿命的死亡率曲线矩形化 跨度。现有的证据表明，CR可以防止某些方面的 灵长类动物的二次衰老与CR相反，运动诱导的热量 缺乏并不能减缓大鼠的原发性衰老，这表明CR的作用 对原发性衰老的影响是通过减少食物的摄入和代谢来介导的， 而不是减少能源供应。在这方面， 本研究的第1阶段是：1）确定实现的可行性 延长20%的能量摄入限制或延长20%的能量增加 运动消耗，超重，50-60岁的女性和男性， 实现遵守CR和锻炼方案所需的技术。 两种方法的有效性将被评估为CR（膳食计划 与代餐）和运动（监督与独立 运动计划）;和2）评估和比较12个月的效果， CR和运动干预对一些潜在的衰老标志物的影响， 身体成分和CAD和2型糖尿病的危险因素。在第一阶段， 志愿者将被随机分配到五组之一：2个CR组，2个运动组， 组和一个对照组。每次干预将有16名参与者 对照组20例，无干预组20例。 根据之前的数据，我们预计辍学率约为25%。 体验.我们的目标是让至少12名女性和12名男性完成1年的 CR，12名女性和12名男性在第1阶段完成1年的运动。的 从本研究第1阶段的前2年获得的信息将 在第二阶段的规划和设计中使用。应该可以更多地 根据以下因素准确估计第2阶段每组的参与者数量： 我们在第一阶段的经验在第2阶段，将有3组健康， 50-60岁的超重男性和女性：CR、运动和对照。公约与建议委员会和 运动方案将根据我们的经验设计， 第一阶段的其他研究者在II期，CR的持续时间和 运动干预将持续两年。

DESCRIPTION: (provided by applicant) Primary aging is the progressive deterioration in structure and function with advancing age that occurs independently of disease and lifestyle/environmental factors. Slowing of primary aging results in an increase in maximal life span. Caloric restriction (CR) slows primary aging in various short-lived organisms, such as guppies, flies, mice and rats. It is not known if CR slows primary aging in humans. Secondary aging is due to disease processes and harmful life-style/environmental factors. Protection against secondary aging results in rectangularization of the mortality curve without an extension of maximal life span. Available evidence suggests that CR protects against some aspects of secondary aging in primates. In contrast to CR, an exercise-induced, caloric deficit does not slow primary aging in rats, suggesting that the effect of CR on primary aging is mediated by decreased intake and metabolism of food rather than by decreased energy availability. In this context, the specific aims of Phase 1 of this study are: 1) To determine the feasibility of achieving prolonged 20% restriction of energy intake or prolonged 20% increase of energy expenditure by exercise, in overweight, 50-60 yr old women and men and refine the techniques needed to achieve adherence to the CR and exercise protocols. The efficaciousness of two approaches will be evaluated for CR (meal plans versus meal replacement) and for exercise (supervised versus independent exercise programs); and 2) To evaluate and compare the effects of 12 mo of the CR and exercise interventions on a number of potential markers of aging, on body composition and on risk factors for CAD and type 2 diabetes. In Phase 1, volunteers will be randomized to one of five groups: 2 CR groups, 2 exercise groups and one control group. There will be 16 participants per intervention group (i.e. 32 CR, 32 exercise) and 20 in the control, no intervention, group. We anticipate a drop out rate of approximately 25% based on previous experience. Our goal is to have at least 12 women and 12 men complete 1 yr of CR, and 12 women and 12 men complete 1 yr of exercise in Phase 1. The information obtained from the first 2 yrs, Phase 1, of this research, will be used in the planning and design of Phase 2. It should be possible to more accurately estimate the number of participants per group in Phase 2 based on our experience in Phase 1. In Phase 2, there will be 3 groups of healthy, overweight men and women aged 50-60 yr: CR, exercise and control. The CR and exercise protocols will be designed on the basis of our experience, and that of the other investigators, in Phase 1. In Phase 2, the duration of the CR and exercise interventions will be two years.