For 75 years, scientists have documented a curious fact: If rats and mice eat 30% to 40% fewer calories than normal, they live 15% to 40% longer than is typical for their species. The observation has offered humans hope that our own maximum life span could one day be extended, enabling people to live well past their 100th birthday.
A new study of monkeys pours cold water on that notion — while at the same time offering some heartening health news.
Among a colony of rhesus monkeys tracked for more than 20 years, animals whose calories were restricted to 30% below normal lived no longer, on average, than monkeys whose eating was unrestricted, scientists found. But the diet did offer clear benefits, notably in warding off cancer.
It appears that "we are seeing a separation between what we call 'health span' from 'life span' — they are not hand in hand," said Rafael de Cabo, an experimental gerontologist at the National Institute on Aging in Baltimore and senior author of the study.
The report, published online Wednesday by the journal Nature, suggests that what has proven true for rodents and various other animals may not hold true for primates — humans included — at least under the conditions that were studied. The findings are likely to disappoint the hundreds of people in the U.S. who practice a strict regimen of calorie restriction in hopes of postponing their appointment with the Grim Reaper.
But the results also have some researchers scratching their heads. The results are quite different from a 2009 study of monkeys in a colony in Wisconsin that found a clear survival edge from age-related diseases like diabetes, cancer and heart disease in calorie-restricted animals. That study also saw a trend toward longer life for monkeys on the diet when all causes of death were considered.
Figuring out whether differences in diet, the animals' genetic makeup or something else caused the results to diverge could offer important clues to the ways in which calorie restriction — and aging — work, De Cabo said.
The new study tracked 121 male and female monkeys at the National Institutes of Health's animal center in Maryland starting in 1987. One group of 35 animals — the "old onset" group — were 16 to 23 years old when the study began. (Rhesus monkeys mature around age 4 or 5 and live to 27, on average, in captivity.) The rest were in a group that included juvenile and adolescent monkeys, as well as younger adults up to the age of 14.
All the monkeys received the same food, but the control animals could eat as much as they wanted during daylight hours. The rest were limited to only 70% of what they ate before the experiment began.
In the older group, there was no overall difference in age of death between calorie-restricted and free-eating animals. That was true when all causes of death were considered together as well as when deaths from age-related illnesses were calculated separately, the authors found.
Longevity under both conditions was above the norm, however. And four of the older animals in the calorie-restricted group and one from the control group have broken rhesus monkey longevity records by living beyond 40 years.
That fact especially intrigues gerontologist Rick Weindruch of the University of Wisconsin in Madison, author of the earlier monkey study.
"To me this is really important — that five animals either reached or exceeded what has been thought to be the maximum life span of the species," Weindruch said.
Among the younger animals, the scientists didn't find any survival edge for dieting animals. But they did find reduced rates of diabetes and stark differences in cancer rates.
So far, no monkey in the calorie-restricted group has been diagnosed with cancer, De Cabo said, whereas six cases have occurred in the controls and are believed to have been the cause of death of five of them. That is in line with rodent studies, which have also found that calorie restriction seems to ward off cancer.
There were other differences too. Calorie-restricted monkeys weighed less and looked younger than the animals that ate freely. They also appeared "younger" in some metabolic respects, with lower blood levels of triglycerides and glucose in the old group and lower cholesterol levels in males of both age classes.
The fact that diseases of old age can be warded off even if life span isn't necessarily extended suggests "that health and longevity are not the same thing," said Steven N. Austad, a biogerontologist at the University of Texas Health Science Center at San Antonio, who wrote a commentary accompanying the report.
This could be considered encouraging, he added: "In the ideal scenario, we'd stay healthy to a relatively decent age and then we'd suddenly fall over at the appropriate time. That would be a good thing. What we don't want is people living longer and longer in worse and worse health."
Scientists aren't sure how to explain why the new study produced different results than the Wisconsin study, in which only 13% of the calorie-restricted monkeys died due to some age-related disease compared with 37% of the control monkeys.
But they have some ideas. Chief among them: The food served was very different, even though the overall amounts of protein, carbohydrates and fats were similar in both studies.
The Wisconsin diet consisted of purified ingredients mixed together and was high in sugar, perhaps explaining why so many of the free-feeding monkeys in that study developed diabetes. The Maryland monkeys ate a diet made from natural ingredients that contained more plant micronutrients and omega-3 fatty acids, among other items.
As a result, all of the monkeys in the new study may have been healthier overall, regardless of whether they were calorie-restricted.
Though the final word on whether calorie restriction extends life span is not in — nearly 50% of the younger monkeys are still alive — the authors wrote that they are unlikely to find a survival edge when all is said and done. But it's still possible they will, De Cabo said, especially if the cancer difference grows starker.
Even if the strategy turns out not to be the elixir of youth, that wouldn't devastate 54-year-old St. Louis resident Joe Cordell, an avid practitioner of calorie restriction for the last 10 years.
"I would like to live to the outer limits of what human beings normally live," said the 5-foot-9, 129-pound lawyer, who eats berries, apple peel and walnuts for breakfast and favors giant salads for dinner.
But, he added, "I would be delighted to take 90 to 95 years without cancer, without heart disease, without diabetes or other chronic illnesses. To me, that would have warranted this."