Caloric restriction improves health and survival of rhesus monkeys

Abstract

Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

Conflict of interest statement

R.W. is a member of the board of LifeGen Technologies, a company focused on nutritional genomics. G.S.R. is Chief Executive Officer of GeroScience, Inc. and Vice President of Prolongevity Technologies. D.K.I. serves as Chief Scientific Officer for GeroScience, Inc., and Prolongevity Technologies, Inc. D.B.A. serves on the board of IKEA and has received consulting fees from multiple government, not for profit, and for profit organizations with interests in obesity and nutrition. None of these activities benefit directly from this research and no competing financial interests are declared. The remaining authors declare no competing financial interests.

Figures

Figure 1. Mortality curves for monkeys at UW and at NIA.

These curves depict data for male and female monkeys on the UW study and on the NIA study. Animals are grouped by age where male J/A include juvenile and adolescent onset animals, female J/A include juvenile and adult onset animals, and old include the advanced age onset animals. Inset boxes indicate animals still alive, dashed line marks 50% mortality. Statistics related to this figure are provided in Supplementary Information, Supplementary Table 1.

Figure 2. Bodyweight data for monkeys at NIA and UW.

(a) Bodyweight (kg) for male and female monkeys at UW and at NIA grouped by age where male J/A include juvenile and adolescent onset animals, female J/A include juvenile and adult onset animals, and old include the advanced age onset animals. Digits shown in white within the boxes are the numbers of individual animals contributing to each data point, data are shown as mean±s.e. of the mean. (b) Comparison of bodyweight averages for monkeys from UW and NIA studies with records of the internet Primate Aging Database (iPAD). Average bodyweight for control and CR monkeys at both study locations were determined by age category including adult (11–13 years of age), late mid-age (18–20 years of age) and advanced age (25–27 years of age). Data are expressed as percent deviation from the iPAD average for females and males from each age category. Statistics related to this figure are provided in Supplementary Information, Supplementary Tables 2 and 3.

Figure 3. Adiposity data for female and male monkeys at NIA and UW.

Percent adiposity (fat (g)/total bodyweight (g)) calculated from DXA (dual energy X-ray absorptiometry) measures conducted during the course of the studies for male and female monkeys at UW and at NIA grouped by age where male J/A include juvenile and adolescent onset animals, female J/A include juvenile and adult onset animals, and old include the advanced age onset animals. Digits shown in white within the boxes are the numbers of individual animals contributing to each data point, data are shown as mean±s.e. of the mean.

Figure 4. Food intake data for monkeys at NIA and UW.

Food intake (daily values in Kcalories) for male and female monkeys at UW and at NIA grouped by age where male J/A include juvenile and adolescent onset animals, female J/A include juvenile and adult onset animals, and old include the advanced age onset animals. Digits shown in white within the boxes are the numbers of individual animals contributing to each data point, data are shown as mean±s.e. of the mean.

Figure 5. Fasting glucose values for monkeys at NIA and UW.

Circulating levels of glucose (mg dl−1) are shown for male and female monkeys at UW and at NIA grouped by age where male J/A include juvenile and adolescent onset animals, female J/A include juvenile and adult onset animals, and old include the advanced age onset animals. Digits shown in white within the boxes are the numbers of observations contributing to each data point, data are shown as mean±s.e. of the mean.

Figure 6. Morbidity curves for monkeys at NIA and UW shown.

(a) Graphs represent the first occurrence of any age-related disease, disorder or condition for combined males and females from UW (top) and NIA J/A (bottom). Statistics related to this figure are provided in Supplementary Information, Supplementary Table 4. (b) Incidence of prevalent age-related conditions in nonhuman primates for control and CR animals from UW and NIA (J/A and old-onset combined). To compare studies, cancer and cardiovascular disorders are reported as incidence upon necropsy and are expressed as a percentage of the animals that are deceased.