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.
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