Beneficial alterations in energy expenditure, glucose metabolism, and cardiovascular health could be major contributors to the life-extending action of dietary restriction. We have shown that dietary restriction causes significant change sin all three of these areas in rhesus monkeys. Long-term changes in one or more of these areas could be extremely important to the overall effect of this intervention. We hypothesize that dietary restriction causes sustained changes in energy expenditure, glucose metabolism, and cardiovascular health which contribute to the retardation of disease and aging. In this renewal, we plan to continue investigating the effect of aging and dietary restriction on composition, we plan to continue measuring changes in body lean and fat mass with aging and dietary body mass. This will be done using several techniques including anthropometrics, dual-energy x-ray absorptiometry (DXA), computer assisted tomography (CT) and isotope dilution.
Specific Aim 2 is to determine the effect of dietary restriction of whole-animal energy expenditure. Energy expenditure will be measured by indirect respiration calorimetry using calorimetry chambers and the doubly labeled water method. The calorimetry experiments will provide estimates of resting energy expenditure, the themic effect of feeding, activity, and total energy expenditure. Body composition data will be used to normalized energy expenditure for comparison between groups and among individuals. In addition to calorimetry derived measurements of activity, motion detectors will be used for further quantification of physical activity.
Specific Aim 3 is to elucidate the effect of dietary restriction on insulin sensitivity and other parameters of glucose regulation by Minimal Modeling and quantitation of insulin receptor abundance. Minimal Modeling is performed on data derived from a frequently sampled intravenous glucose tolerance test and insulin receptor abundance will be measured in biopsies of skeletal muscle.
In Specific Aim 4, we will further examine the effects of dietary restriction on composition and properties of plasma LDL that may affect their proteoglycan-binding and thus their atherogenicity, using blood samples, and in vitro systems for assessment.
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