Caloric restriction delays disease onset and mortality in rhesus monkeys

Abstract

Caloric restriction (CR), without malnutrition, delays aging and extends life span in diverse species; however, its effect on resistance to illness and mortality in primates has not been clearly established. We report findings of a 20-year longitudinal adult-onset CR study in rhesus monkeys aimed at filling this critical gap in aging research. In a population of rhesus macaques maintained at the Wisconsin National Primate Research Center, moderate CR lowered the incidence of aging-related deaths. At the time point reported, 50% of control fed animals survived as compared with 80% of the CR animals. Furthermore, CR delayed the onset of age-associated pathologies. Specifically, CR reduced the incidence of diabetes, cancer, cardiovascular disease, and brain atrophy. These data demonstrate that CR slows aging in a primate species.

Fig. 1

Animal appearance in old age. (A–B) Photographs of a typical control animal at 27.6 years of age (~age of average lifespan). (C–D) Photographs of an age-matched animal on CR.

Fig. 2

Longitudinal study design and mortality curves. (A) Study design. Initial group of 30 males and groups of 30 females and 16 males added in 1994. Hash marks represent deaths. (B) Age-related mortality. Animals that died from non-age-related causes are excluded. (C) All-cause mortality. These curves depict data for animals which died from any cause.

Fig. 3

Effect of CR on age-associated disease. (A) Incidence of three major age-related conditions. Hash marks represent age of diagnosis. Individual animals with multiple discrete diagnoses are represented multiple times. (B) Data represent first occurrence of any age-related disease in each individual animal.

Fig. 4

Effects of CR and age on loss of GM in the brain. (A) Statistical parametric map of the t-contrast (SPMt) displayed on coronal slices depicting regions where an age-related decrease in GM volume was observed. (B) plot of the age effect on GM volume at the labelled location in (A). (C) SPMt indicating regions where CR monkeys exhibited preserved volume relative to controls. (D) Notched box plots for each group at the location labelled in (C) indicating the mean (center line), the 95% confidence interval (notches) and the 5^th, 25^th, 75^th and 95^th percentiles (horizontal lines) representing the range of variability in the data. (E) SPMt depicting regions where the slope between GM volume and age differs as a function of group. (F) Scatter plot of the location labelled in (E). All comparisons included sex and total brain volume as covariates. The probability threshold for each t contrast was p<0.005 (uncorrected). The color bars represent the value of the t-statistic in panels A, C and E. The left side of the brain is on the left in the images.