Eric Ravussin’s solution to volunteers straying from their dietary regimen is to accommodate them at the Pennington Biomedical Research Center in Baton Rouge, Louisiana. The center is set up with a “metabolic kitchen” which ensures the diets are of good quality and calorically accurate.
Ravussin reported results of an intervention study designed to assess the benefit of calorie restriction, or a combination of calorie restriction and exercise, on 48 healthy but overweight male and female volunteers who spent the first 3 months and last 2 weeks of a 6-month study at the center.
The volunteers were split into four groups. In one, calories were reduced to 25 percent of that required to keep the subjects' weight stable. The second group was put on mild caloric restriction (12.5 percent of that required to maintain weight), plus enough physical activity to soak up another 12.5 percent of their calories. In a third, a very low-calorie diet (LCD) was designed so that 15 percent of body weight would be rapidly lost, but then the volunteers would be allowed to consume enough calories to maintain that weight. A fourth group, with no intervention, served as controls.
Not unexpectedly, except for the control group, all of these volunteers lost weight. Those in the intervention groups also had lower plasma insulin than did controls (33, 24, and 10 percent lower for the CR, CR plus exercise, and LCD groups, respectively). All the groups demonstrated a 25-30 percent improvement in insulin sensitivity. Though magnetic resonance imaging revealed that there was no difference in levels of muscle fat among the four groups, those on intervention had up to 50 percent lower fat in the liver.
Ravussin and colleagues are also set up to measure cellular parameters that might shed some light on what changes occur during calorie restriction. They found, for example, that spontaneous oxidation of DNA was lower in the three intervention groups compared to controls, though they detected no difference in protein carbonyls, which herald protein oxidation. Ravussin and colleagues also have ongoing microarray analysis of protein expression in muscle and adipose tissue, and they are examining the effects of CR on mitochondrial biogenesis. They found, for example, that levels of the mitochondrial protein PGC1α are increased in the CR and LCD group, but not in the CR plus exercise group. They also found that levels of SIRT1, a protein that has been implicated in longevity in yeast, and mammalian cells (see ARF related news story), are elevated almost twofold in the CR volunteers.
Ravussin reported that volunteers in all the intervention groups had a lower 24-hour energy expenditure than would be expected, even correcting for body weight. This suggests that there has been some metabolic adaptation to the caloric restriction. The basis for this is currently being investigated.
But what about humans who live to ripe old ages? Is there any correlation between longevity as we know it now, and caloric intake? There just might be. Bradley Willcox from the Pacific Health Research Institute, Honolulu, Hawaii, showed some data from the world’s longest-running population-based study on centenarians, the Okinawan Centenarian Study.
The islands of Okinawa are home to the highest concentration of centenarians in the world. The people there also have the longest disability-free life expectancy in the world, reported Willcox. So why is that?
Willcox suggested that there may well be some genetic influence because siblings of Okinawan centenarians generally live longer, too. But he also emphasized the role of diet. Historically, Okinawa has been the most undernourished prefecture in Japan, and data from the Okinawan Centenarian Study supports the theory that reduced caloric intake has contributed to their longevity. Okinawans have had the lowest average body weight of all Japanese, for example, and levels of DHEA, which inversely correlates with caloric intake in animal studies, are much higher in male and female Okinawans than in age-matched Americans, Willcox reported.
However, things are changing in Okinawa. Unfortunately, Okinawans now rank as some of the heaviest Japanese, so unbeknownst to many people from that prefecture, they may be taking part in one of the largest studies to date on caloric intake and longevity. Should Okinawa also lose its standing in the centenarian tables, one might conclude that it is because they are spending more time at the dinner table. Only time will tell.—Tom Fagan.