Caloric Restriction and Healthy Life Span: Frail Phenotype of Nonhuman Primates in the Wisconsin National Primate Research Center Caloric Restriction Study

Abstract

Calorie restriction without malnutrition increases longevity and delays the onset of age-associated disorders in multiple species. Recently, greater emphasis has been placed on healthy life span and preventing frailty than on longevity. Here, we show the beneficial effect of long-term calorie restriction on frailty in later life in a nonhuman primate. Frail phenotypes were evaluated using metabolic and physical activity data and defined using the Fried index. Shrinking was defined as unintentional weight loss of greater than 5% of body weight. Weakness was indicated by decline in high intensity spontaneous physical activity. Poor endurance or exhaustion was indicated by a reduction in energy efficiency of movements. Slowness was indicated by physical activity counts in the morning. Low physical activity level was measured by total energy expenditure using doubly labeled water divided by sleeping metabolic rate. Weakness, poor endurance, slowness, and low physical activity level were significantly higher in control compared with calorie restriction (p < .05) as was total incidence of frailty (p < .001). In conclusion, we established a novel set of measurable criteria of frailty in nonhuman primates, and using these criteria, showed that calorie restriction reduces the incidence of frailty and increases healthy life span in nonhuman primates.

Figure 1.

Group comparisons for each component of the Fried phenotype. Open bars represent C animals; closed bars represent CR animals. Data are shown as mean ± standard deviation (SD) Analysis was conducted using unpaired student’s t-tests *p < .05, **p < .01.

Figure 2.

Group and sex comparisons for each component of the Fried phenotype. Open bars represent male animals; closed bars represent female animals. Data were analyzed using two-way analysis of covariance (ANCOVA) with diet (C vs CR) and sex (male vs female) as between-subject factors.

Figure 3.

The presence of Fried frailty phenotype in C and CR groups. Open bars represent C animals, closed bars represent CR animals. Bars indicate the number of subjects per group presenting with the number of phenotypes identified on the x-axis. Animals with no frailty phenotypes are defined as not frail, 1–2 phenotypes are prefrail, and 3–5 phenotypes are frail. The prevalence of nonfrail, prefrail, and frail between the C and CR groups were compared by chi-square test.