Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys

Abstract

Caloric restriction (CR) without malnutrition increases longevity and delays the onset of age-associated disorders in short-lived species, from unicellular organisms to laboratory mice and rats. The value of CR as a tool to understand human ageing relies on translatability of CR's effects in primates. Here we show that CR significantly improves age-related and all-cause survival in monkeys on a long-term ~30% restricted diet since young adulthood. These data contrast with observations in the 2012 NIA intramural study report, where a difference in survival was not detected between control-fed and CR monkeys. A comparison of body weight of control animals from both studies with each other, and against data collected in a multi-centred relational database of primate ageing, suggests that the NIA control monkeys were effectively undergoing CR. Our data indicate that the benefits of CR on ageing are conserved in primates.

Figure 1. Mortality curves.

(a) Age-related mortality. Animals that died from non-age-related causes are excluded. The Cox regression detected a statistically significant effect of CR in increasing survival (P=0.007) with a HR of 2.89 (95% CI: 1.34–6.25). (b) All-cause mortality. These curves depict data for all animals on the study not censored for cause of death. The Cox regression detected a statistically significant effect of CR (P=0.037; Fig. 1b) with an estimated HR of 1.78 (95% CI: 1.04–3.04).

Figure 2. Body weight comparisons.

(a) Body weights for male and female control animals from UW and NIA studies. Males, 10–12 years: NIA=6, UW=15; 24–33 years: NIA=7, UW=4. Females, 12–18 years: NIA=20, UW=15; 21–25 years: NIA=5, UW=8. Data are shown as average±s.e.m. *P<0.05 (Welch’s t-test). (b) Comparison of body weights for control animals on UW and NIA rhesus monkey ageing and CR studies with national averages for age- and gender-matched animals. Data shown in (a) are presented as per cent deviation from averages for males aged 10–12 years (175 animals, 2,790 data points), males aged 24–33 years (114 animals, 11,805 data points), females aged 12–18 years (334 individuals, 18,626 data points) and females aged 21–25 years (255 animals, 15,666 data points).