In a long-awaited study, underfed monkeys didn't have longer life spans, raising doubts that severe calorie restriction could result in extended lives for most animals and possibly humans.
In research going back more than 75 years, a sharp reduction in caloric intake has been associated with increased longevity. The initial work was done with mice and rats, but was later corroborated in other laboratory subjects such as fruit flies and worms, raising hopes that it would apply to humans.
But those hopes are being dimmed by the results published online by the journal Nature. The National Institute on Aging study, begun in 1987, involved rhesus monkeys, which are much closer to humans, both genetically and in average longevity, than previous test subjects.
The scientists, led by Julie Mattison, were surprised to find that calorie restriction -- the treated monkeys ate 30 percent fewer calories than those in the control group -- didn't affect life spans.
It did confer some health benefits, reducing the incidence of cancer and diabetes. It slightly raised the incidence of cardiovascular diseases.
The monkeys were started on their restricted diets either when the animals were young or in middle age. Now, more than two decades later, about half the monkeys that were underfed from a young age are still alive -- the same as in the control group. The scientists calculated, with a probability of 99.9 percent, that the calorie-restricted animals will not survive longer than the animals in the control group. The monkeys that were already older when they were put on the diet have all died. The oldest died at 40, the same as for the corresponding control animals.
These results conflict with a 2009 study, conducted at the Wisconsin National Primate Research Center. Although scientists there did not find that calorie restriction had a significant effect on life span, they did report a trend toward longer life and healthier aging for some of the treated monkeys.
Things were going well for the treated monkeys at the beginning of the National Institute on Aging study, but around the time the Wisconsin researchers published their work, "we noticed that for our monkeys, things were not going so well," Mattison said. The treated animals started dying at the same rate as the controls.
Both Mattison and Ricki Colman, the researcher who was the lead author of the 2009 paper, stressed that their studies weren't meant to compete with each other and that they had many differences, including diet composition, treatment of diseases and ages of the animals at the beginning of the experiments. Both studies will keep going until all the animals die.
But Mattison acknowledged that the primate research hadn't fulfilled the high expectations of the rodent research. In the rodent studies, "you would reduce caloric intake by 10 or 20 percent and increase life span by the same amount," she said. "But in primates and probably humans, things seem to be much more complicated."
The effectiveness of some substances thought to mimic the positive effects of caloric restriction has been questioned by scientists such as Matt Kaeberlein at the University of Washington. But even with the latest data, Kaeberlein thought it was still too early to dismiss calorie restriction entirely. "There are still reasons to be optimistic that caloric restriction or drugs mimicking its beneficial effects will enhance healthy aging in people," he said.