Long lived dieting monkeys

Rhesus monkey. He can teach us a lot about aging, for real. Credit: J.M Garg

Dieting is a commonly used term in our society (especially if you’re a woman), even when most times it is not done with the aim of improving our health but our appearance. As anyone who’s ever suffered a diet knows, dieting is anything but easy however, the reward is immense. So immense that actually cutting down on our energy intake can lead to healthier, longer lives.

How? You might ask. Caloric restriction (CR, a term almost akin to dieting in terms of reduced calorie intake) has been shown to lead to a considerable increase in longevity and improved healthspan. Even though the potentials of such an intervention have been found in a number of animal models, the only 2 CR studies performed to date in primates (rhesus monkeys) showed diverging results. To be able to determine the reason behind these differences in findings, a recent longitudinal re-analysis of both has been performed and recently published.

If you want to live long and healthy, better forget these portions. Credit: user Siqbal

These two early studies focused on the impact of CR in healthy male and female rhesus monkeys, which are not only highly similar to humans at the gene level, but also in the phenotypic effects of aging. The first study at the National Institute on Aging (NIA) involved 121 monkeys; and the other at the University of Wisconsin Madison (UW) 76 monkeys. While the first study did not show any significant effects of CR on survival and close-to-significance health improvements, the UW study showed important beneficial effects on health and survival.

Among the uncovered differences, were differences to study design. In the NIA study there were different age groups and the feeding model involved a 30% restriction of food intake in the CR group in comparison to control group (ad libitum, without restrictions) while in the UW one, CR did not start until adult age and the CR protocol was individualized, as model for implementation in humans. Moreover, the origin of the animals was also different, and with it their genetic make-up, which might have an undetermined impact on results.

Diet composition was another diverging factor: in comparison to the UW diet, the NIA diet was lower in fat, higher in protein and higher in fibre. Moreover, the nutrient content of the diets was also different. Feeding times and procedures were also different, even when housing conditions were comparable.

Performing a new analysis on survival rates in both studies showed that for UW CR still showed significant positive effects on survival, whereas in NIA in the young age groups an increased mortality in comparison to control-fed animals could be found, pointing to deleterious effects of CR during early years. Differences among studies were also found with respect to gender differences, where in the NIA study female mortality was higher, probably due to untreated endometriosis (in contrast, in the UW study, females were treated for the condition reducing mortality thereby). When it comes to weight effects of intervention, in general in UW, and the young age NIA male monkeys under CR had a consistent lower weight than controls, which was not seen in females or old-age NIA monkeys.

Other parameters affected by age and where an impact of CR was observed was adiposity (all UW monkeys and at NIA for juvenile/adult males only). Moreover, a distinct impact of age on adiposity and fasting glucose levels was found between control and CR monkeys. With respect to age-related diseases such as cancer, diabetes or cardiovascular disease in both CR groups (UW and NIA) a reduced incidence of such diseases was found in comparison to controls.

In summary, data from both studies suggest that the CR paradigm is effective in delaying the effects of ageing in nonhuman primates but that age of onset is an important factor in determining the extent to which beneficial effects of CR might be induced, not too soon but also not too late. That is to say that if we are to extrapolate results to humans, for a real positive effect on healthspan and longevity, caloric restriction should be implemented in the adult age, past the growth phase but also before old age.

Mattison et al. Caloric restriction improves health and survival of rhesus monkeys. Nature Communications 8, Article number: 14063 (2017)

Further reading:

Colman, R. J. et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204 (2009).

Mattison, J. A. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321 (2012)