For centuries, explorers searched for the elusive fountain of youth. More recently, scientists have joined the hunt for a way to slow the aging process and extend the limits of longevity. Some researchers say they’ve found it.

For years, in fact, investigators have been aware of a sure-fire way to put the brakes on aging and, in some cases, almost double lifespan. In 1935, a team of Cornell University nutritionists discovered that mice fed one-third fewer calories than normal lived about 40 percent longer than mice eating as much as they wanted. Since then, scientists have tested a Noah’s ark of creatures—from yeast cells and fruit flies to monkeys. In almost every study, calorie restriction increases life expectancy and protects against a host of chronic diseases. Well into old age, animals typically remain more active and younger-looking, as well. Why?

“Frankly, all we have are guesses at the moment,” says Eric Ravussin, PhD, a researcher at Louisiana State University’s Pennington Biomedical Research Laboratory, one of three research centers where calorie restriction diets are now being tested in human volunteers. One theory holds that when calorie intake falls short, cells sound an alarm, switching their priorities from reproduction to repair and maintenance, fending off genetic damage and the wear and tear caused by the effects of unstable oxygen molecules.

Controlling this switch is a class of genes called sirtuins, which affect how energy is delivered to cells. In a 2006 experiment straight out of science fiction, University of California, San Francisco biochemistry researcher Cynthia Kenyon, PhD, tinkered with the equivalent gene in roundworms. The result: a mutant species with a lifespan six times longer than normal.

Three large studies—at Washington University in St Louis, Pennington Biomedical Research Center in Baton Rouge, and Tufts University in Boston—are underway to test calorie restriction in human volunteers. Preliminary findings are encouraging. In 2007 researchers at Washington University reported that calorie restriction improved heart function and lowered inflammation levels in a group of volunteers—two signs that could mean better health and longer life down the road. In a study of 48 men and women Eric Ravussin and his colleagues found that after six months, volunteers on a diet that cut calories by 25 percent, reduced their insulin levels and their core body temperature—two changes associated with longevity. They also had fewer signs of the kind of chromosomal damage that is associated with aging and cancer.

In September, scientists from the National Institute on Aging and Louisiana State University reported more encouraging findings in the online journal PLoSOne. Their study showed that calorie restriction in human volunteers increased sirtuin proteins and factors in the blood that protect cells against heat and stress. The findings also showed that alternate day fasting may be even beneficial than daily calorie restriction.

Peter Voss, an expert in artificial intelligence who runs a start-up firm in Los Angeles, has been conducting his own calorie restriction experiment since 1997. He has cut total calories by about one-third from what he was eating before, down a total of just 1850. Five foot 10 inches tall, his weight at the time was 155. He now weighs 130. His blood pressure, good to begin with, resembles that of an active teenager, about 100/60. His triglyceride and cholesterol levels are rock bottom.

In the beginning Voss scrupulously counted calories and checked the nutrient labels on everything he ate. Now he simply monitors his progress by keeping his weight stable at 130. Voss’s diet is Spartan by any standard. Steel-cut oatmeal with fruit and milk are a special treat. But Voss insists that he isn’t hungry all the time. “I eat whenever I feel like it,” he said. Instead of reaching for chips or a cookie for a snack, however, he crunches a carrot or a red pepper. At restaurants, he sticks with appetizers or a first-course salad. His girlfriend, a marathon runner, is also on a calorie restriction diet, which probably helps him stick with the program.

Voss maintains a website about his own experiences with calorie restriction at (www.optimal.org).

There are downsides. Voss is now so thin that sitting on a hard chair gets uncomfortable. But he insists he still has all the energy he needs to work the 14 or 15 hours a day required by his start-up company, and to squeeze in an hour or so of power walking most days. Calorie restriction reduces testosterone levels, which in men can mean lower libido. (So few women have voluntarily taken up calorie restriction that researchers don’t have much data about the way it affects their hormones.)

Not everyone is convinced that calorie restriction will buy humans much extra time. The average Japanese male consumes about 2300 calories a day. Men on nearby Okinawa consume about 17 percent fewer calories a day—very close Peter Voss’s 1850—but they live only a little less than a year longer. Calorie restriction may have its most dramatic effects in species that have experienced periodic famines, forcing them to evolve extreme measures to shut down reproduction and focus on staying alive until food supplies return. We humans, naysayers argue, aren’t likely to be among them.

And then there are practical issues. It’s hard enough to get people to make the changes that are already proven to increase the odds of a long and healthy life, like eating more fruits and vegetables and whole grains and exercising half an hour a day. Not many people are likely to stick with a program that means going hungry or fasting completely every other day. Indeed, people around the world are consuming more calories than ever—and packing on the pounds.

Still, if you’re interested in buying yourself more time by eating less, check out the Calorie Restriction Society’s website at www.calorierestriction.org. The advice you’ll find there may sound familiar. Avoid simple sugars and flours. Eat lots of green leafy and other vegetables. Replace saturated fat with unsaturated and omega-3 fats.

If more of us followed that advice, even if we never bothered to count a calorie, we’d be healthier for it.

And probably add years to our lives.

Tags: alternate day fasting, calorie restriction, longevity, sirtuins