CALORIE RESTRICTION AND AGING IN NON-HUMAN PRIMATES

在啮齿类动物中，它可以延缓衰老过程。 最成功的做法是减少 热量摄入减少25- 40%。 这种减少，无论是早推出 无论是在生活中还是在中年， 显著延长寿命。 此外，在正常的系统中， 生理性衰老已经得到很好的表征，热量限制 已经被证明可以降低与年龄相关的变化率。 为 研究表明，营养不良的小鼠保持胸腺组织质量和免疫功能， 能力更长，自发性癌症更少。 同样地， 其他老化的生化标志物（如胶原蛋白变性 速率、旷场行为、毛发生长速率等）有利地 影响。 这些观察结果的意义将是巨大的 如果它们适用于更高的物种，则具有实际意义。 也许在人类身上还没有完成类似的研究， 由于饮食依从性的不确定性和 生存 然而，非人类灵长类动物将适合这种情况。 调查 在目前的提案中，我们计划仔细 评价30只恒河猴（macaca mulatta）的饮食 限制程序。 最初，所有动物将被置于 定义明确的实验饮食。 经过三个月的精心 饮食观察一半的动物将有一个渐进的 减少卡路里（在随后的3个月内），以及 此后，将维持在约70%的水平， 饮食前水平。 受限制的膳食成分将是 碳水化合物和脂肪，而蛋白质含量，矿物质和 维生素将保持稳定。 另一组将是 继续自由进食。 尽管恒河猴的年龄 大约是人类的两倍，衰老过程的改变， 而不是生存将是实验性的措施。 到 为了实现这一目标，我们开发了一组老化的“生物标志物”， 这与年龄和寿命都有很好的相关性。 这些测量包括某些生理参数，其中 我们已经证明了与年龄相关的变化（免疫 功能、视觉调节和葡萄糖调节）。 目标 这项研究的目的是确定中年饮食限制是否 恒河猴将与延迟的客观标志物相关， 衰老 如果这是真的，它将使更大的意义， 对以下益处的全面和充分描述的观察 低等物种的热量限制。

In rodent species it has been possible to retard aging process(es). This has been most successfully accomplished by the reduction of caloric intake by 25-40%. Such reduction, whether introduced early in life or in midlife, has been repeatedly demonstrated to significantly prolong life. Furthermore, in system in which normal physiologic aging has been well characterized, caloric restriction has been shown to diminish the rate of age-related change. For examine, underfed mice maintain thymic tissue mass and immune competence longer and have fewer spontaneous cancers. Similarly, other biochemical markers of aging (such as collagen denaturation rate, open field behavior, hair growth rate, etc.) are favorably affected. The implications of these observations would be of great practical importance if they are applicable to higher species. Similar studies have not been accomplished in humans, perhaps because of the uncertainty of dietary compliance and length of survival. Nonhuman primates, however, would be suitable for such investigation. In the current proposal we plan to carefully evaluate 30 rhesus monkeys (macaca mulatta) in a dietary restriction program. Initially, all animals will be placed on a well defined experimental diet. After three months of careful dietary observation one half of the animals will have a gradual reduction in calories (over the subsequent 3 months), and thereafter be maintained at a level of approximately 70% of their pre-diet level. The dietary components restricted will be carbohydrates and fats, whereas protein content, minerals and vitamins will be maintain stable. The other group will be continued on an ad-libitum diet. Although the rhesus monkey ages at about twice the rate of humans, alterations in aging processes, rather than survival will be the experimental measures. To accomplish this, we have developed a panel of "biomarkers" of aging which correlate well with both chronologic age and longevity. These measures include certain physiological parameters in which we have demonstrated characteristics age-related changes (immune function, visual accommodation, and glucose regulation). The goal of this study is to determine if midlife dietary restriction in rhesus monkeys will be associated with objective markers of delayed aging. If this is true, it would lend greater significance to the thorough and well characterized observations of the benefits of calorie restriction in lower species.