CALORIE RESTRICTION AND AGING IN NON-HUMAN PRIMATES

在啮齿动物物种中，已经有可能延缓衰老过程。 最成功地实现这一点的方法是减少 卡路里摄入量减少25%-40%。这样的削减，无论是否及早推出 无论是在生活中还是在中年，都一再证明 显著延长寿命。此外，在正常的系统中 生理性衰老有很好的特征，卡路里限制 已经被证明可以降低与年龄相关的变化的速度。为 检查，喂养不足的小鼠维持胸腺组织质量和免疫 能力更长，自发性癌症更少。同样， 衰老的其他生化标志(如胶原变性 速率、开阔地行为、毛发生长速度等)都是有利的 受影响。这些观察结果的影响将是巨大的。 如果它们适用于高等物种，则具有实际意义。 也许，类似的研究还没有在人类身上完成。 由于饮食依从性和持续时间的不确定性 生死存亡。然而，非人灵长类动物适合这样做。 调查。在目前的提案中，我们计划谨慎地 在饮食中评估30只恒河猴(猕猴) 限制程序。最初，所有动物都将被放在一个 明确的实验饮食。经过三个月的谨慎 饮食观察一半的动物会有逐渐的 减少卡路里(在随后的3个月内)，以及 此后保持在大约70%的水平 节食前水平。限制的饮食成分将是 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 继续进行临时节食。虽然恒河猴会衰老 衰老过程中的变化速度大约是人类的两倍， 而不是生存将是实验措施。至 为了做到这一点，我们开发了一组衰老的“生物标记物” 这与实际年龄和寿命都有很好的相关性。 这些措施包括某些生理参数，其中 我们已经表现出与年龄相关的变化的特征(免疫 功能、视觉调节和血糖调节)。目标是 这项研究的目的是确定中年饮食限制在 恒河猴会与延迟性疾病的客观标志物相关 衰老。如果这是真的，它将赋予 对以下好处的全面和有特色的观察 低等物种的卡路里限制。

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.