ABSTRACT
In a longitudinal study of the effects of moderate (70%) dietary restriction (DR) on aging, plasma glucose and insulin concentrations were measured from semiannual, frequently sampled intravenous glucose tolerance tests (FSIGTT) in 30 adult male rhesus monkeys. FSIGTT data were analyzed with Bergman's minimal model, and analysis of covariance revealed that restricted (R) monkeys exhibited increased insulin sensitivity (S(I), P < 0.001) and plasma glucose disappearance rate (K(G), P = 0.015), and reduced fasting plasma insulin (I(b), P < 0.001) and insulin response to glucose (AIR(G), P = 0.023) compared with control (C; ad libitum-fed) monkeys. DR reduced the baseline fasting hyperinsulinemia of two R monkeys, whereas four C monkeys have maintained from baseline, or subsequently developed, fasting hyperinsulinemia; one has progressed to diabetes. Compared with only the normoinsulinemic C monkeys, R monkeys exhibited similarly improved FSIGTT and minimal-model parameters. Thus chronic DR not only has protected against the development of insulin resistance in aging rhesus monkeys, but has also improved glucoregulatory parameters compared with those of otherwise normoinsulinemic monkeys.
Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Type 2/physiopathology , Diet, Reducing , Energy Intake , Hyperinsulinism/physiopathology , Insulin Resistance/physiology , Insulin/blood , Macaca mulatta/growth & development , Aging , Analysis of Variance , Animals , Body Mass Index , Body Weight , Disease Progression , Fasting , Glucose Tolerance Test , Homeostasis , Insulin/metabolism , Insulin Secretion , Male , Models, Biological , Time FactorsABSTRACT
Dietary restriction (DR) retards aging and extends the maximum lifespan of laboratory mice and rats. To determine whether DR has similar actions in a primate species, we initiated a study in 1989 to investigate the effects of a 30% DR in 30 adult male rhesus monkeys. In 1994, an additional 30 females and 16 males were added to the study. Although the animals are still middle-aged, a few differences have developed between the control and DR animals suggesting that DR may induce physiologic changes in the rhesus monkey similar to those observed in rodents. Fasting basal insulin and glucose concentrations are lower in DR compared to control animals while insulin sensitivity is higher in the restricted animals. DR has also altered circulating LDL in a manner that may inhibit atherogenesis. These results suggest that DR may be slowing some age-related physiologic changes. In addition to measures of glucose and lipid metabolism, the animals are evaluated annually for body composition, energy expenditure, physical activity, hematologic indices, and blood or urinary hormone concentrations. In the next few years, the first animals will reach the average lifespan ( approximately 26 years) of captive rhesus monkeys and it will become possible to determine if DR retards the aging process and extends the lifespan in a primate species.
Subject(s)
Aging/physiology , Diet , Animals , Behavior, Animal , Blood Glucose/metabolism , Body Composition , Body Weight , Bone Density , Dehydroepiandrosterone/blood , Energy Metabolism , Female , Hydrocortisone/blood , Insulin/blood , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor I/metabolism , Leptin/blood , Lipids/blood , Macaca mulatta , Male , Melatonin/urine , Physical Exertion , Time Factors , Triiodothyronine/bloodABSTRACT
The ability to compensate for acute water deprivation was studied in young adult (YA, 7-9 years), middle aged (MA, 13-17 years), and older adult (OA, 20-36 years) rhesus monkeys of both sexes (N = 6/group). Water intake and urine volume were measured during three 7-day trials: 3 days of baseline measurement, 1 day of deprivation and 3 days of compensation. OA drank less during baseline (380 +/- 63 mL/day) than MA (679 +/- 92 mL/day, p < 0.05) or YA (750 +/- 128 mL/day, p < 0.01). All groups drank more following deprivation than at baseline and the OA drank significantly less than the younger groups (both p < 0.01), but the increase above baseline did not differ among groups when expressed as a cumulative percentage of baseline (89% for OA; 77% for MA; 83% for YA). Urine volume of all groups decreased by similar percentages on the day of deprivation (56% overall) and this reduction represented a similar proportion (58% overall) of baseline water intake. Urine concentration increased significantly during deprivation (p < 0.05) and returned to baseline values during compensation with no differences among age groups. OA water balance appears to have been maintained at lower levels of intake and excretion. In conclusion, responses to acute hydrational challenges in the elderly should be interpreted in the context of customary fluid intake.
