During the first phase, teams of researchers ran small-scale pilot experiments to answer a variety of questions including, what kind of calorie restriction could study participants actually stick to? To this end, some of the pilot studies tested a diet-only calorie reduction, others tested exercise only, and others tested half-diet, half-exercise. Another question posed by the researchers: What level of calorie restrictions would have an impact on biomarkers of aging? Aging biomarkers are simple biological measurements that differentiate longer-lived people -- those who celebrate birthdays into their 90s and 100s -- from people who live the average life expectancy, Redman said. "We know that longer-lived individuals are able to sustain lower blood sugar levels and lower levels of insulin and have lower core body temperature levels in comparison to people who don't live as long as them," she said. After the pilot studies, the National Institute on Aging committed to funding larger phase two CALERIE studies at three universities: Pennington in Baton Rouge, Washington University in St. Louis and Tufts University in Boston.
At Pennington, Redman and her colleagues focused on reducing calories by 25% through diet alone. Women between 25 and 45 and men between 25 and 50 were recruited; about half were normal weight and the other half overweight but not obese. Throughout the study, participants ate what they liked, yet they also took vitamins and supplements to ensure that their diets were "nutritionally adequate," Redman said. Each participant was also given a scale. Instead of calculating daily calories and slashing them by 25%, weight loss was used to estimate the total reduction in calories for each participant over time.
However, the participants did not hit the 25% reduction as anticipated, Redman said: "People achieved 15% calorie restriction, actual, over the two years." No matter. The results from this lesser calorie restriction amount were "pretty remarkable," she said. For example, participants lost an average of about 20 pounds each by the end of the first year and maintained that loss during the second year. "The calorie-restrictive diet also caused a reduction in sleeping metabolic rate by about 10%," Redman said. This remained true after one year, when weight loss peaked, and after two years, when weight remained constant.
A slowed metabolism means the body has become more efficient in using fuel -- whether from food or oxygen -- to derive energy. "It's important because every time we generate energy in the body, we generate byproducts," Redman said. These byproducts of normal metabolism, also called oxygen radicals, accumulate in the body and over time cause damage to cells and organs, she explained. And this damage is "what has been linked to a shortened lifespan," she said.
Not only did calorie restriction slow the metabolism of participants, lower levels of oxidative damage were seen when measured by a compound in urine. Calorie restriction, then, mimicked some of the healthy aging signposts seen in long-lived individuals, Redman said.
The "big breakthrough" with this study, said biologist John R. Speakman
of the University of Aberdeen in Scotland and the Chinese Academy of Sciences in Beijing, is that it is the first randomized controlled trial of calorie restriction in humans. Randomized, controlled trials, in which participants are divided by chance into groups to compare interventions, are considered more valuable to scientists than other types of experiments. Speakman, who did not participate in the research but he served on the data safety and monitoring board for the CALERIE project, explained that all previous studies of calorie restriction in humans have been on a voluntary basis."It has been known since the 1930s that calorie restriction reduces the rate of aging and extends lifespan in rodents," Speakman said. Since then, studies in different animals show the same general pattern -- with some exceptions. "For example, it doesn't work in houseflies," he said. "Plus, the monkey literature is a bit confusing." For this reason, the new study's "big contribution" is that participants showed two key changes previously observed in calorie-restricted rodents: lowered metabolic rate and reduced production of radical oxygen species, Speakman said. That said, the level of calorie restriction achieved in the new study was "rather modest compared to that used in rodents and other animals," he said. "This really shows the difficulties in doing calorie restriction work on humans." However, a strength of the new research is that it "included extensive measurements of the individual responses."
Exactly how calorie restriction prevents aging, Speakman says "is the million-dollar question." The research supports two theories of longer life: the "rate of living" (lower metabolism) and reduced oxidative damage. However, the study shows a correlation only, he said, "so we can't infer that these changes are causally linked to reduced aging. Nevertheless, it is a step forward to indicate that these two ideas are not rejected by the current research."
Going forward, Redman wants to reconvene the study participants to see whether they're maintaining calorie restrictions and lowered metabolic rates. She also wants to study a group of people from early in their lives until death so she can see the possible long-term results of restricted calorie intake.
It's not only the diet, she repeated. It's true that the people who see more sunrises than most of us eat less -- and more healthy -- calories than in a Western diet, Redman said. "But what's important is they're living longer and they're free of chronic disease."