Can the lifespan of an animal be increased by restricting their intake of calories? The question has been the subject of study for decades, primarily through two concurrent long-term experiments using rhesus monkeys. Interestingly, these two studies came to conflicting conclusions, but by comparing their results and accounting for other variables, scientists have now determined that the answer is yes – caloric restriction does help monkeys stay healthier and live longer.
Caloric restriction is about eating less in general, but it requires the right balance because going too far in the other direction can lead to malnutrition and a potential loss of muscle mass and bone density. The practice needs to be carefully controlled by scientists, and when done properly it has been shown to improve the life expectancy of rats, worms, fish and some species of yeast.
On the road to figuring out whether or not it could eventually be applied to humans, scientists began studying the effects of caloric restriction on primates. In 1987, the National Institute on Aging (NIA) began its study, feeding a test group of rhesus monkeys 30 percent less food than a control group of animals of the same age, sex and size. In 1989, the University of Wisconsin-Madison (UW) launched a similar study.
After 20 years, the UW team reported positive results, having found that the monkeys whose diets had been restricted were living longer on average, and had less instances of cancer, cardiovascular disease and insulin resistance. But when the NIA study announced its findings in 2012, the researchers reported the diet had no significant effect on the monkeys' longevity, although it did make them generally healthier.
"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," says Rozalyn Anderson, a corresponding author on the study.
To try to reconcile the discrepancies between the two studies, scientists from both teams collaborated to analyze data gathered in both experiments, involving close to 200 monkeys in total. The researchers were able to identify several factors, including age, diet and sex, that may have influenced the differing results.
First up, monkeys in the NIA study were of varying ages, with young, adult and older animals in both the test and control groups. Meanwhile, the UW study only experimented with adult monkeys of around eight years old. Although rodent studies have shown that starting the process early in life improves the animals' health, in primates beginning too early can have detrimental effects on the normal growth of the monkeys.
What the monkeys ate contributed to the differences as well. The NIA monkeys were fed a naturally-sourced diet, while the food at UW was semi-purified, so it could be monitored and remain consistent throughout the study. While seasonal variation could occur in the NIA diet, it was generally higher in protein and fiber, and lower in fat, than at UW. As a result, control monkeys at UW were fatter than those at NIA.
Sex is another factor, where male rhesus monkeys appear to be more at risk of the ill health effects of obesity than females, and the researchers believe this would translate to humans. Other factors, like the specific species of the monkeys, where they were born, and the differences in the daily feeding routines between studies, could all also affect the outcomes.
With the datasets of both studies pooled together, results that weren't clear in the smaller sample size of each individual study become more obvious patterns. The NIA study reported no difference between the control and test groups for older-onset monkeys, but when compared to the wider context of the UW study, a benefit emerges: the NIA monkeys ate less than the UW control group and showed subsequently improved survival rates.
Taking these factors into account, the combined study concludes that "lower food intake in adult or advanced age is associated with improved survival in nonhuman primates," with one old-onset male, currently 43 years old, holding the longevity record for his species.
The research was published in the journal Nature Communciations.
Source: University of Wisconsin-Madison
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