The latest findings from a 25-year study published in Nature Communications suggest that monkeys on a caloric-restricted diet live longer and have reduced age-related diseases than peers who are allowed to eat what they want.
The study, which started in 1989 at the University of Wisconsin-Madison (UW), is one of two long-term US research projects examining the effects of caloric restriction on non-human primates.
What is surprising, is that these latest findings from Wisconsin appear to contradict those of the other project, an equally long study from the National Institute of Aging (NIA), that found no difference in survival between control-fed and caloric-restricted monkeys.
Writing in Nature in August 2012, the NIA researchers concluded that the two factors that have the biggest impact on lifespan are good genes and eating a healthy, balanced diet. Study leader and gerontologist Don Ingram, who designed the study 30 years ago while at the NIA, said he found it remarkable that people might think a simple decrease in calories could have such an effect.
The two studies are considered important because apart from them, the only other research into possible links between caloric restriction and longevity has been confined to non-primate organisms.
Such studies have suggested restricting calorie intake while continuing to supply essential nutrients can extend the lifespan of yeast, flies and rodents by up to 40%.
The possibility of a link between caloric restriction and reduction in age-related disease and mortality has intrigued scientists for a long time, as corresponding author and assistant professor of geriatrics at UW, Rozalyn Anderson, explains:
"We study caloric restriction because it has such a robust effect on aging and the incidence and timing of age-related disease. Already, people are studying drugs that affect the mechanisms that are active in caloric restriction. There is enormous private-sector interest in some of these drugs."
Scientists are more interested in the underlying biology of caloric restriction
The monkey on the left was kept on a restricted diet, while the one on the right was allowed to eat as much as he wanted. Researchers found monkeys in the latter group had a three-fold increased risk of death.
Image credit: Jeff Miller/UW-Madison
Richard Weindruch, a professor of medicine at the UW School of Medicine and Public Health, and one of the founders of the Wisconsin project, says their study is important because it shows the biology seen in lower organisms is relevant to primates. Plus, it may offer a lead into drugs or other treatments to slow the onset of disease and death.
Public interest in caloric restriction started about 20 years ago, when some individuals set out to cut their calorie intake by 30% to slow the diseases of aging. But, as Prof. Anderson explains, the Wisconsin and NIA studies are more interested in the underlying biology:
"We are not studying it so people can go out and do it, but to delve into the underlying causes of age-related disease susceptibility. It's a research tool, not a lifestyle recommendation, but some people get caught up: 'What if I did caloric restriction?'"
For the Wisconsin study, Prof. Anderson and colleagues have been following the progress of 76 rhesus monkeys at the Wisconsin National Primate Research Center in Madison since they entered early adulthood between 7 and 14 years of age.
The monkeys have been eating a diet reduced in calories by 30%. Meanwhile, another group of monkeys has been eating a diet where they can eat as much as they want.
Monkeys that ate what they wanted had three-fold increased risk of death
The results show that, compared with the caloric-restricted monkeys, the comparison monkeys had a 2.9 times higher risk of disease and a three-fold increased risk of death.
Speaking about the discrepancy between their result and the NIA project's findings, co-author and senior scientist Ricki Colman, who presently co-leads the Wisconsin project, suggests the control monkeys on the NIA project, who were fed according to a standardized food intake chart designed by the National Academy of Science, were probably also on a restricted calorie diet, as he explains:
"In Wisconsin, we started with adults. We knew how much food they wanted to eat, and we based our experimental diet on a 30% reduction in calories from that point.""At all the time points that have been published by NIA, their control monkeys weigh less than ours, and in most cases, significantly so," he adds.
While there is healthy competition between the two projects, there is also collaboration to extract the maximum amount of science from them, since the projects costs millions of dollars, run over decades and are unlikely to be repeated. Prof. Anderson explains:
"We are now working with the NIA scientists to perform a comprehensive analysis of all of our data, taking into consideration the differences in study design, genetics, time of origin and composition of the diet. It's possible that insights we could not get from the individual studies will emerge from this aggregate data."
The UW team believes that many of the effects on aging and disease of restricting calorie intake are to do with how the body regulates energy: it reprograms metabolism, affects how fuel is used and how the organisms respond to changes in the environment as they age.
They give the example of diabetes - a disease that damages fat, muscle, blood vessels and even how the brain works. Diabetes can be regarded as "an inability to properly respond to nutrients," says Anderson.
Anderson and colleagues began to see diabetes in the comparison monkeys while they were still in their prime, within 6 months of the start of the study. There was a stark contrast between the comparison monkeys - who could eat what they wanted - and the caloric restricted monkeys.
Until 2 years ago, there was no evidence of diabetes in the caloric restricted monkeys, while the comparison group included a significant number of animals with diabetes, pre-diabetes and metabolic syndrome.