New research may dampen the enthusiasm of anyone looking to extend their lifespan by restricting their caloric intake. Though laboratory rats on calorie-restricted diets can live up to 35 percent longer than their gluttonous counterparts, and previous research on rhesus macaques hinted at modest increases in longevity for dieting primates, data from a long-term prospective study on macaques paints a more nuanced picture.
Published today (August 29) in Nature, research performed at the National Institute on Aging (NIA) suggests that calorie restriction may provide some health benefits, but does not increase lifespan more than a sensible diet.
The finding “is probably an indication that the paradigm for [calorie restriction] work will have to be reshaped,” said William Swindell, a geneticist at the University of Michigan who did not participate in the research.
Increased longevity has been a hallmark of calorie restriction—the reduction of caloric intake by 10 to 40 percent—since the early 20th century, when researchers first began to restrict the diets of laboratory animals, including rats, mice, and nematode worms. More recently, scientists have also focused on health benefits, showing that restraining caloric intake can decrease incidence of type II diabetes and cancer. However, “there were reasons to believe [benefits from lower animals] might not translate to humans,” said NIA researcher Julie Mattison. Monkeys live much longer than lab rats and mice, and in contrast to the much-studied inbred rodents, are genetically diverse, like humans.
In the late 1980s, groups at the University of Wisconsin and the NIA set up two separate studies investigating the effects of long-term calorie restriction on rhesus macaques, whose average lifespan is about 27 years in captivity. The University of Wisconsin group published their 20-year results first, in 2009. After deaths from non-age-related causes, like anesthesia, were removed from analysis, they saw that control monkeys were 3 times more likely to die of age-related causes than calorie restricted (CR) animals. Fewer CR monkeys fell ill with cardiovascular disease, cancer, or diabetes.
In contrast, the newly released NIA results show no difference in mortality between CR and control monkeys. Though reason for these conflicting results remains unclear, one possibility is differences in the CR diets used and variation in the monkeys’ access to food. The Wisconsin group created a diet of mostly purified nutrients, and allowed their control monkeys unrestricted access to food during daylight hours. Not surprisingly, the control group became overweight. NIA, on the other hand, fed their monkeys a diet of mostly whole foods and restricted food access to control monkeys as well, ensuring that they remained at healthy weights.
The Wisconsin study “is more modeling the unfortunate state of obesity,” said Colman, “but if you put the studies together, they’re modeling a pretty broad range [of monkey diets].”
The varied genetics of the monkeys may also be playing a role in the different longevity outcomes seen, said Swindell. A closer look at mouse research suggests that not all mouse strains respond to CR by living longer: some live the same average time, and some actually die earlier, Swindell noted.
Longevity differences aside, the two studies found remarkably similar health benefits of CR monkeys. Both found that monkeys on CR diets were less likely to develop tumors, showed reduced evidence of cardiovascular disease, and had better blood sugar control. Both studies have also found evidence that calorie restriction slows brain aging. The Wisconsin researchers found that age-related brain atrophy is lessened in CR monkeys, while the NIA group previously published that a CR regimen helps prevent symptoms of Parkinson’s disease in macaques.
“I love fact that in a lot of ways what we say really is the same,” said Ricki Colman, first author on the Wisconsin group’s 2009 paper. Colman pointed out that although CR-promoted longevity may get the most attention, possible health benefits are more important. “The point is not to live forever, but live a healthier life,” he said. “That’s what most people are after.”
In the NIA project, however, the researches divided the monkeys into “young-onset” CR macaques, who started caloric restriction between 1 and 14 years old, and “old-onset” CR monkeys, who started CR between 16 and 23 years of age, and found that health benefits depended on the sex and age of CR enrollment. Old-onset male monkeys had lower triglycerides and cholesterol, while young-onset CR monkeys did not show these benefits. When the NIA team looked at cancer, diabetes, arthritis, and cardiovascular disease together, they found no differences between old-onset monkeys and controls; only young-onset CR monkeys seemed to benefit, falling ill later in their lives.
For now, both primate studies will continue, and researchers at NIA and the University of Wisconsin are beginning to collaborate to understand which variables, like diet composition and genetics, are most important in determining CR’s health effects.
Much aging research has “ignored health and focused on longevity,” said Steven Austad of the University of Texas Health Science Center San Antonio, who wrote the Nature commentary on the study but was not involved in the research. The NIA “monkeys got less diabetes and cancer, yet didn’t translate this didn’t translate to longer life,” he said, suggesting that these two effects can—and should—be separated.
“The studies are still ongoing,” Colman noted. “We don’t have the final answers yet.”
J. Mattison et al., “Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study,” Nature, doi: 10.1038/nature11432, 2012.