Slash your food intake and you can live dramatically longer—at least if you're a mouse or a nematode. But a major study designed to determine whether this regimen, known as caloric restriction, works in primates suggests that it improves monkeys' health but doesn't extend their lives. That outcome contradicts a similar study of monkeys reported 3 years ago.
Researchers not involved with the new paper say the results are still encouraging. Although the monkeys didn't evince an increase in life span, "both studies show a major improvement in 'health span,'" or the amount of time before age-related diseases set in, says physiologist Eric Ravussin of the Pennington Biomedical Research Center in Baton Rouge. "I certainly wouldn't give up on calorie restriction as a health promoter" based on these findings, adds molecular biologist Leonard Guarente of the Massachusetts Institute of Technology in Cambridge.
For many species, eating between 10% and 40% less than normal not only prolongs life, but also improves metabolic measures such as insulin sensitivity and defers age-related ailments such as cancer and heart disease. Scientists haven't nailed down what happens to humans on this extreme diet. The first randomized study, the 2-year CALERIE trial, wrapped up earlier this year. Ravussin, who is one of the trial's leaders, says that the final results haven't been analyzed, but in 2011, he and a colleague revealed that 6 months of calorie cutting reduced the participants' risk of cardiovascular disease by 28%.
Testing whether calorie restriction also stretches human life span is impractical, however, so more than 20 years ago, scientists put two groups of rhesus monkeys (which have an average life span of about 27 years) on skimpy rations. In 2009, researchers reported in Science that a group of monkeys at the Wisconsin National Primate Research Center in Madison was reaping the benefits of the diet. Eating less cut rates of cancer and heart disease by half, for example. More than 50% of the animals were still alive, but the team detected a survival trend. Although overall mortality was the same, only 13% of the calorically restricted monkeys had died from age-related conditions, versus 37% of the control animals.
Those findings jibe with most of the results from the second group of monkeys, which have been living and dying at the National Institutes of Health Animal Center in Dickerson, Maryland. "I think this [report] is quite positive," says senior author Rafael de Cabo, a gerontologist at the National Institute on Aging in Baltimore, Maryland. For instance, the team found that none of the Maryland monkeys that started calorie restriction when they were young have developed cancer. De Cabo and colleagues reveal online today in Nature that dieting monkeys also showed lower blood levels of triglycerides, which influence the risk for cardiovascular disease. But a disparity between the groups emerged when the team analyzed longevity. About half of the animals are still alive, so the researchers don't have definitive life span data. However, the famished monkeys don’t appear to be living longer than control monkeys that ate more.
One possible cause of the discrepancy, de Cabo says, is a difference in the animals' diets. The Maryland monkeys noshed on more healthful food that included plenty of complex plant compounds, whereas the Wisconsin monkeys consumed processed food high in refined sugar. Control animals in Wisconsin also ate more than control animals in Maryland, which may even be slightly calorically restricted, de Cabo says. He notes that calorie restriction produces a bigger effect on longevity "if the control group is couch potatoes."
Genetic variability between the groups could also be a factor. The Maryland group was more diverse, including Indian and Chinese animals, whereas the Wisconsin monkeys all came from India. Studies of other organisms have shown that genetic differences between individuals can affect the response to calorie restriction, notes molecular biologist Matt Kaeberlein of the University of Washington, Seattle, who wasn't involved with the research.
For now, gerontologist Richard Weindruch, who heads the Wisconsin monkey project, isn't ready to give up on a longevity effect. He notes that some control and calorically restricted animals in the Maryland group surpassed by several years what researchers thought was the maximum life span for the species, about 40 years. That suggests the animals' diets do increase how long they can live, he says.
Researchers will have better answers in 10 years or so, when the last animals in both groups have died.