NYTimes.com – The Calorie-Restriction Experiment:

A curious aspect of the Calerie project, though, is that it is not meant to study weight loss or if one type of diet is better than another. Instead, Calerie is investigating how (and if) a spartan diet affects the aging process and its associated diseases. To the Calerie researchers, these are quite distinct. The aging process, which researchers sometimes call “primary” or “intrinsic” aging, refers to the damage that ordinarily accumulates in our cells as we grow older, a natural condition that seems to have limited the maximal lifespan of humans to 120 years. Diseases that accompany the aging process — often called “secondary aging” — are those afflictions increasingly prevalent in the elderly, like cancer, diabetes and cardiovascular disease.

There seems little doubt that calorie restriction can have significant effects on secondary aging. A recent spate of papers in some of the world’s leading medical journals demonstrate that in small studies, human subjects following such diets experience astounding drops in cardiovascular risk factors; a forthcoming review on cancer risks in animals with such diets, moreover, suggests a stark correlation — fewer calories mean fewer tumors. This explains why the stakes for Calerie are high. Essentially, the study asks whether calorie restriction allows people to grow older in better health — with less disease, fewer drugs and shorter hospital stays — through a method that neither medicine nor scientific technology have yet come close to approximating. Meanwhile, the experiment aims to shed some light on the more complex and still-unsettled question of whether calorie restriction affects primary aging, and thus longevity, in humans. Going back more than a half century to an experiment at Cornell University in the mid-1930s, calorie restriction has been shown again and again to extend the lives of mice, rats and other animals. An ongoing experiment at the University of Wisconsin on rhesus monkeys, which began in 1989, portends similar results: compared with normal-weight primates on a regular calorie regimen, the monkeys on restricted diets are healthier and more vigorous and seem destined (at least at the moment) for a longer life.

A clinical trial that follows human subjects through their entire lives, much as the primate study in Wisconsin does, would be impossible. For one thing, it would be ethically problematic to restrict calories in children (though with animals, the earlier that calorie restriction begins, the longer they live). For another, we already live a long time now, thanks to advances in medicine, surgery and public health, so “if you wanted to do longitudinal studies in humans, it would take 125 years,” Eric Ravussin, who leads the team doing the Calerie experiment at Pennington in Baton Rouge, told me. Thus the researchers in the two-year study are instead looking at changes in what they call biomarkers. A decline in Doug Hansen’s core internal temperature, for instance, would suggest a slowdown in his primary aging process (data from a respected study on aging shows individuals with lower temperatures generally live longer). Other characteristics related to secondary aging are just as important. As Hansen curtails his calories for the next 18 months, doctors and medical technicians will measure, among other variables, inflammation, insulin levels and blood pressure. Reductions in any of these things would indicate a lessened vulnerability to heart disease and diabetes.

Another problem humans present is their susceptibility to temptation. Primates and mice are kept in cages and eat what they are fed; none have ever had to choose to forswear a spring roll or a cupcake. The medical literature on calorie restriction sometimes cites an experiment conducted in Minnesota in the 1940s to study the effects of starvation, especially with the war-torn populations of Europe in mind. The men — all lean to begin with, all volunteers (they were conscientious objectors to World War II) — were subjected to about a 40 percent decrease in caloric consumption. The state of near starvation led a few of the subjects to the threshold of insanity. They became irritable and depressed; some began to lie and cheat; at least one engaged in acts of self-mutilation. Some of the potential insights of the Calerie study, therefore, are psychological as much as physiological. If ordinary Americans want to cut their energy intake by a more modest 25 percent — whether to slow down the aging process or seek a pharmaceutical-free way to reduce the risks of, say, cardiovascular disease — can they actually do it? The feasibility of long-term food reduction has never been adequately investigated. “Here there are really three things we want to know,” Susan Roberts, a professor of nutrition and psychiatry who is in charge of the Calerie team at Tufts, told me. “The first is, can we really implement human caloric restriction? The second is, can we really implement it in a way that doesn’t neglect the biology? People can’t walk around hungry, so is hunger a necessary part of the biology of calorie restriction? The third is, are there unacceptable side effects that you wouldn’t pick up in animals that you would pick up in humans?” Roberts went on to say: “And if we found that caloric restriction was healthy and everyone can do it? The goal of the trial is to see if this is ready for prime time.”

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