Objective To test the hypothesis that moderate dietary restriction will slow the rate of functional aging as assessed by regular assessments of the monkeys in terms of body size and composition, glucose tolerance and insulin sensitivity, and energy expenditure. We are testing the hypothesis that moderate restriction of food intake will not only reduce the incidence and delay the onset of age-related diseases, but will also slow the rate of aging and prolong lifespan of primates, as has been shown for rodents and some other species. Adult rhesus monkeys are being assessed semi-annually in terms of body size and composition, insulin levels and blood glucose regulation, metabolic rate, and other measures as a component project of a Program Project Grant. After collection of baseline data, half of the animals underwent gradual food restriction so that they now eat 30% less than their individual baseline amounts, adjusted for changes (decreases) in levels of voluntary intake by the control subjects. After 60 months of restriction for Group 1 we find that animals on DR weigh less and have less body fat than controls, have increased insulin sensitivity, lower fasting insulin levels and insulin increments in response to glucose and tolbutamide challenges, lower fasting glucose levels and improved glucose tolerance, and reduced oxygen consumption. These differences between groups that have been observed thus far are consistent with the hypothesis that DR without malnutrition will improve metabolic efficiency and slow the rate of functional aging. Interim data analyses are in progress as the project continues. During the current report period we added 30 adult female and 16 adult male rhesus monkeys to the study to be evaluated in ways similar to those used for the initial group. These animals were given their baseline assessmemnts, restriction was imposed on the experimental groups, and six-month assessments were completed during this report period. Key words aging, dietary restriction, lifespan extension
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