Nonhuman primate calorie restriction

Abstract

Calorie restriction (CR) is the only dietary intervention that repeatedly extends both median and maximal lifespan in a broad range of species. Although there has been considerable interest in CR and its ability to retard aging, the mechanism has remained elusive. In contrast to studies in rodent and nonmammalian systems that are now beginning to provide mechanistic insights into how CR promotes longevity, the efficacy of CR in delaying primate aging has yet to be fully demonstrated. Here we review some of the insights from CR studies in short-lived species. We describe the advantages of using the rhesus monkey as a model for human aging and detail how CR can be successfully implemented in this species. We discuss the findings from our ongoing longitudinal study and outline the effects to date of CR on rhesus monkey health. Finally, we highlight the importance of primate studies in the context of aging research and its potential to advance our understanding of human aging and health.

FIG. 1.

Calorie restriction (CR) is not mechanistically equivalent to lifespan extension by genetic manipulation leading to reduced insulin signaling. The insulin/insulin-like growth factor signaling pathway has been implicated in regulating longevity in numerous species. Transgenic, knockout, and mutant genetic variants have demonstrated that reduced signaling through this axis can increase lifespan in yeast (glucose signaling pathway), worms, flies, and mice. Studies of CR in these species reveal that there is evidence to support reduced signaling through this axis as an outcome of CR, but that the pathways for lifespan extension are not identical and that other factors distinct from insulin/insulin-like growth factor play a role in the mechanism of CR.

FIG. 2.

Captive rhesus monkey survival curve. Percent survival in normally fed captive rhesus monkeys at the Wisconsin National Primate Research Center. Median survival is ∼26 years of age, 10% survival is ∼35 years of age, and maximum survival is ∼40 years of age (20).

FIG. 3.

Food intake in control and CR animals. Food intake data are collected daily for each animal and averaged over a 6-month period. Food intake in CR animals is ∼30% less than their own individual baseline levels. Control animals are represented by closed circles and CR animals are represented by open circles. The drop in food intake during the first 2 years is assumed to be related to the switch from standard laboratory chow to the experimental diet. Data are presented as group mean ± standard error of the mean (SEM). All data are analyzed using a longitudinal repeated measures design as detailed previously (65).

FIG. 4.

DXA-measured total body fat and lean mass in control and CR animals. Differences in fat mass between control and CR animals account for the majority of the difference in body weight between the diet groups. Control animals are represented by closed circles and CR animals are represented by open circles. Data are presented as group mean ± SEM. All data are analyzed using a longitudinal repeated measures design as detailed previously (22, 23).

FIG. 5.

Glycosylated hemoglobin measurements in control and CR animals. Glycosylated hemoglobin is a measurement of long-term glucose control. Control animals are represented by closed circles and CR animals are represented by open circles. Data are presented as group mean ± SEM. All data are analyzed using a longitudinal repeated measures design as detailed previously (35).

FIG. 6.

Insulin sensitivity index in control and CR animals. Insulin sensitivity index values calculated by the minimal model approach for data collected by a frequently sampled intravenous glucose tolerance test. Control animals are represented by closed circles and CR animals are represented by open circles. Data are presented as group mean ± SEM. All data are analyzed using a longitudinal repeated measures design as detailed previously (35).