Study addresses controversy on caloric restriction's effect on longevity and health

Rozalyn Anderson, PhD

A long-awaited report from a collaboration between researchers at University of Wisconsin-Madison and the National Institutes of Health-National Institute on Aging (NIH-NIA) shows that restricting calories does indeed help rhesus monkeys live longer, healthier lives.

Two rhesus monkey studies initiated in the 1980s, one based at UW-Madison (involving 76 monkeys) and the other based at NIH-NIA (involving 121 monkeys), had investigated the effect of a 30 percent reduction in calories on parameters of health. Factors that the groups measured included incidence of cancer, cardiovascular disease, and insulin resistance, as well as morbidity and mortality. While the UW-Madison study found significantly longer lifespan and improved health for monkeys on caloric-restricted (CR) diets, the NIH-NIA team found no significant difference in survival. Health parameters in the NIH-NIA experimental monkey group showed a trend toward improved outcome, but did not reach statistical significance. The same statistical analysis team at the University of Alabama at Birmingham had analyzed data from both experiments.

“These conflicting outcomes had cast a shadow of doubt on the translatability of the caloric-restriction paradigm as a means to understand aging and what creates age-related disease vulnerability,” said Rozalyn Anderson, PhD, associate professor, Geriatrics and Gerontology.

Dr. Anderson and Ricki Colman, PhD, senior scientist from the Wisconsin National Primate Research Center, in collaboration with researchers from NIA/NIA intramural program, conducted in-depth analysis of data from both studies and experimental differences between the investigations. The results, which were published on January 17, 2017 in Nature Communications, show that caloric restriction does indeed delay aging in nonhuman primates. The authors went on to detail several methodological aspects that scientists believe resulted in conflicting outcomes.

Notably, there were differences in ages of the monkeys involved in the study. Monkeys in the NIH-NIA study were enrolled in the experiment either at a young age (prior to adulthood) or when already at advanced age. In contrast, researchers at UW-Madison initiated caloric restriction only in adult monkeys that had grown to full stature. Comparative analysis revealed that eating less is beneficial in adult and older primates but is not beneficial for younger animals. This is a major departure from prior studies in rodents, where starting at an earlier age is better in achieving the benefits of a low-calorie diet.

Additionally, there were differences feeding practices between the locations. The old-onset NIH-NIA control monkeys voluntarily ate less than the UW-Madison control group, and this lower food intake was associated with improved survival compared to the Wisconsin controls. The lack of difference in survival between old-onset control and CR at NIH-NIA was matched by a lack of difference in bodyweight. Interestingly, further statistical analysis suggests that small differences in food intake in primates could meaningfully affect aging and health.

Importantly, there were marked differences in dietary composition between the two studies. Monkeys in the NIH-NIA study received a diet from natural sources, while the UW-Madison study used a semi-purified diet. As a result, while monkeys at both locations experienced similar caloric density, at normal levels of food intake the higher fat and higher purified sugar diet at UW resulted in greater adiposity (fat) in control fed animals.

Lastly, researchers noted sexual dimorphism in the relationship between adiposity and risk for diabetes (elevated fasting glucose). Evidence from longitudinal data from both studies suggested that female rhesus monkeys were less vulnerable to adverse effects of increased adiposity than males.

The publication has received international media attention, and paves the way for future investigation into the mechanism of how caloric restriction prevents age-related disorders in primates. While age, sex, and diet composition all must be factored in, caloric restriction does seem to be a viable approach to affect aging in monkeys—and most likely humans as well.

“What you eat and how much you eat influences how you age. At the end of the day, it's eat less, weigh less, live longer,” said Dr. Anderson.