Caloric Restriction and Aging in Humans

原发衰老是指结构和功能随着年龄的增长而逐渐恶化，这种现象独立于 疾病和生活方式/环境因素。初级衰老的减缓会导致最大寿命的增加。卡路里 限制(CR)可减缓各种短命生物的初级衰老，如孔雀鱼、苍蝇、小鼠和大鼠。它不是 已知CR是否延缓人类的初级衰老。二次衰老是由于疾病过程和有害的生命- 风格/环境因素。防止二次老化导致死亡率曲线长方化 而不会延长最大寿命。现有证据表明，CR可防止某些方面的 灵长类动物的次级衰老。与CR相反，运动引起的热量缺乏并不能减缓大鼠的初级衰老， 提示CR对初级衰老的影响是通过食物摄取和代谢减少而不是通过 能源供应减少。在这方面，本研究第一阶段的具体目标是：1)确定 实现长期限制20%的能量摄入或延长20%的能源消耗增长的可行性 在超重的情况下，锻炼50-60岁的女性和男性，并改进所需的技术，以实现对CR的坚持 和锻炼计划。两种方法的有效性将针对CR(用餐计划与用餐)进行评估 替代)和锻炼(监督和独立锻炼计划)；以及2)评估和比较 12个月的CR和运动干预对一些潜在的衰老标志物的影响，对体成分的影响 以及冠心病和2型糖尿病的危险因素。在第一阶段，志愿者将被随机分成五组之一：2 CR 两组，2个运动组和1个对照组。每个干预组将有16名参与者(即32名CR，32名 运动)，对照组20人，不干预。根据之前的数据，我们预计退学率约为25% 经验。我们的目标是至少有12名女性和12名男性完成一年的CR，12名女性和12名男性 完成1年第1阶段的练习。从本研究的前2年第1阶段获得的信息将是 用于第二阶段的规划和设计。应该可以更准确地估计参与者的数量 根据我们在第一阶段的经验，在第二阶段，将有三组健康、超重的男性 50-60岁女性：CR、运动和对照。CR和演习方案将在以下基础上设计 我们和其他研究人员的经验，在第一阶段。在第二阶段，CR和锻炼的持续时间 干预措施将是两年。

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 ~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.