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Human Study Shows Benefits of Caloric Restriction

Those on calorie-restricted diets are less prone to heart disease and diabetes, says Washington U. researcher John Holloszy.

There is ample evidence that a severe low-calorie diet can increase longevity in a number of animals, including flies and rodents. But does it work in humans? Scientists at Washington University in St. Louis are hoping to answer that question by studying a group of people – 35 members of the Calorie Restriction Society – who eat around 1,800 calories a day in an effort to improve their health and extend lifespan.

John O. Holloszy, M.D., professor of medicine at the Washington University School of Medicine in St. Louis, has shown that people who eat a very low-calorie diet are protected against heart disease and diabetes. (Credit: Washington University School of Medicine.)

It will be years before the study, which began four years ago, determines how the diet affects lifespan. But John Holloszy and his collaborator Luigi Fontana have already found that those following such a calorie-restricted diet – they call themselves “CRONies” (Caloric Restriction with Optimal Nutrition) – are protected against some diseases associated with aging, such as cardiovascular disease and Type 2 diabetes. The researchers are now planning a larger trial, in which people eating an average diet will reduce their caloric intake by 25 percent, to determine how caloric restriction leads to biological changes over time.

Holloszy talked with Technology Review about his current findings at the 35th annual meeting of the American Aging Association in Boston this week.

Technology Review: What’s the most striking finding you’ve seen in those following a calorie-restricted diet so far?

John Holloszy: They are powerfully protected against the diseases of old age, such as heart disease. They have low levels of cholesterol and triglycerides and extremely low blood pressure – similar to a young child, around 100/60. As a result of the low blood pressure, they have less strain on the arteries, which are much more elastic than usual for people of their age. Their hearts resemble the heart of a person 17 years younger. They also have very good insulin sensitivity, so they are not going to get Type 2 diabetes.

TR: What about their levels of inflammation? That is another factor that’s been the focus of a lot of aging research in the last few years.

JH: As we get older, we get an increasing amount of inflammation, which is probably a very important part of the aging process. CRONies have very low levels of inflammation. C reactive protein, for example, is a marker and cause of inflammation. An average value for a middle-age person is about 2.5; but CRONies have levels of 0.2. It’s just amazing.

TR: So are these people going to live longer?

JH: Caloric restriction definitely does slow secondary aging, which is linked to lifestyle and disease. Smoking, for example, causes secondary aging of the lungs and skin. It’s impossible to say if they’ll increase their maximum lifespan. But I’m sure they’ll live longer than they would if they didn’t do caloric restriction.

TR: You also compared them to a group of runners to see how caloric restriction measures up to exercise.

JH: Yes. We studied a group of master athletes, who are the thinnest group of people eating regular diets that we could find. They were very lean, but not as thin as the CRONies. It’s hard to find anyone that thin, unless they’re sick.

TR: So how do they measure up?

JH: Caloric restriction has greater benefits than exercising, especially on blood pressure and inflammation.

TR: Now you are planning a new trial of caloric restriction?

JH: Yes. The CRONies study was just a cross-section. We don’t know what these people were like before they started caloric restriction. In the new study, we will recruit people who are normal to slightly overweight. We’ll ask them to eat 25 percent less than they ate before. The idea is to have people do this for two years, but that will be very difficult.

TR: What do you hope to show?

JH: At the end of two years, will these people have undergone the same biological changes as rats and mice on caloric restriction? We won’t be able to say they will live longer, but at least we’ll be able to see if the same underlying changes are taking place.

We’ll also be able to determine the maximal level of caloric restriction. For all we know, CRONies are overdoing it. Maybe you can get the same benefits with a smaller decrease in calories.

TR: One question in aging research is whether scientists can design drugs that mimic the health effects of caloric restriction (see “The Fountain of Health”). Will these studies help that goal?

JH: It will give us information on the types of biomarkers we should be looking for. If a mimetic causes the same biological changes, we can say they’re working like caloric restriction.

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