A recipe for longer life?  

Radical diets help mice. Now, the human frontier

By Alice Dembner, Boston Globe Staff  |  August 17, 2004

So strong is the lure of immortality that hundreds of Americans are nearly starving themselves in the hope of gaining a few extra healthy decades. Amid an era of super-sizing, these extreme dieters are following a blueprint from animal research that shows cutting calories about 40 percent below normal dramatically extends average lifespan.

A drumbeat of studies in yeast, worms, flies and mice are unlocking the secrets behind this fountain of youth, and boosting efforts to find a pill that will mimic the effects of such sharp restrictions.

There is no proof yet, however, that ''caloric restriction" will extend life for humans. The first controlled study in people is under way at Tufts University and two other sites, with preliminary results about the diet's safety expected this fall.

But the lack of certitude hasn't stopped people from experimenting on themselves. About 2,000 enthusiasts are members of the Calorie Restriction Society, a California-based group that promotes the Spartan diet as offering immediate health benefits and supports those who try it. The group's president, Brian Delaney, a Scituate native who now lives in Stockholm, estimates that about 200 to 300 members have cut their consumption by at least 30 percent while others are restricting food to a lesser degree. The key to success, according to the society, is consuming just enough essential nutrients, such as vitamins, minerals, fat, protein and carbohydrates.

Julie Lockhart of Dunstable, a grandmother and freelance software-quality engineer who joined the group late last year, said she wants to continue competing in triathlons through age 90. And if she can live in health to 140, all the better.

''I don't want to be sick," said Lockhart, who doesn't want to disclose her current age. ''I don't want to be feeble. I want to be the mistress of my own destiny."

Already spare at 5 feet 5 inches and 120 pounds, she limits herself to a nutrient-dense mix of vegetables and lean proteins totaling about 1,600 calories a day. Lunch, for example, is typically a heaping plate of roasted vegetables with a side of bean chili. That meal plan puts her about 20 percent below what she previously ate, she said, and at least 30 percent below a typical adult woman who gets as much exercise -- 90 minutes to two hours a day.

When she goes out to dinner, she orders a normal meal and eats only a third of it. ''It's a little harder when I visit people," she said. ''I generally request a smaller portion. I will not be rude."

If the pattern in animals holds for people, Lockhart may be able to dodge many diseases of aging, including heart ailments, diabetes and cancer. A survey last year of 18 similar enthusiasts who had restricted their diets for three to 15 years found that many had significantly lowered their blood pressure, cholesterol and blood sugar.

Lockhart already had a healthy diet, but said she feels even better now. She hasn't had a cold since severely restricting her diet a year ago, she sleeps more soundly and she has more than enough energy for work, triathlons, and a twice-weekly, pick-up basketball game with younger teammates.

''I used to be one of those people who get up groggy," she said. ''Now I'm the Energizer bunny. Life is exciting. Why would I not want to be around for as long as possible?"

Lockhart said she gets hungry as mealtime approaches, but has no ill effects from the eating restrictions. Others, however, especially those who have cut their calories by 40 percent or more, complain of constant hunger, moodiness and loss of libido. Women may also stop menstruating.

Delaney gave up on a 40 percent reduction a few years ago after he dropped to 129 pounds on his 5-foot-11-inch frame.

''I was much healthier, I felt great. I just didn't like being that skinny," said Delaney, 41, who now weighs 140 and eats about 1,850 calories a day, roughly 25 percent less than normal. ''Most people don't stick with an extreme version of this diet for very long."

Research in animals has found that the biggest life extension -- as much as 50 percent -- comes from starting a strict restriction in young adulthood and continuing it throughout life. But there is evidence that starting in midlife and cutting calories by only 10 to 20 percent yields a benefit, albeit smaller. Likewise, new research in mice shows fasting every other day, while eating normally in between, also increased average lifespan.

The promise of the diet, coupled with the sacrifice required to follow it, is spurring scientists to seek a pill that produces a similar effect. In a paper published last month in the online version of Nature, Harvard Medical School molecular geneticist David Sinclair and colleagues showed that a substance found in red wine and some vegetables appears to trigger the same mechanisms as caloric restriction in fruit flies and worms, and increases lifespan by about 20 percent without causing lethargy or infertility. Sinclair reported the same effect in yeast last summer.

''We're tricking the animals," Sinclair said, ''into thinking they're running out of food," which activates a gene that appears to play a big role in longevity by slowing the death of cells and enhancing the body's ability to repair damaged cells. The gene was discovered by Sinclair's former mentor, Leonard Guarente, an MIT molecular biologist.

Scientists, who are still uncovering exactly how the process works, believe the effects of caloric restriction are an evolutionary response to allow creatures to survive during adversity and live long enough to reproduce when conditions improve. The stress caused by mild famine may strengthen the cells and allow them to withstand other stresses better and longer.

Guarente recently reported that caloric restriction triggers a release of stored fat, which may tell the body ''it's time to hunker down for survival." In addition, he suggests caloric restriction may spur the body to become more efficient at using nutrients. Other researchers are studying whether caloric restriction boosts immunity, or reduces the creation of ''free radicals," molecules formed during food metabolism that can harm the body.

Meanwhile, 142 people in Greater Boston, Louisiana and St. Louis are restricting their calorie intake between 10 and 30 percent in a government-funded study designed to determine how much can be safely cut and whether health improves. The one-year pilot phase ends this fall and is likely to be followed by a longer experiment.

Monique Hawkins, a 37-year-old real estate developer from Arlington who volunteered for the Tufts-based study, said the 30 percent restricted diet was a lot of work because of all the label-reading and measuring. At 5 feet 7 inches, she was allowed 1,700 calories, down from the 2,400 she had been eating. Initially, she craved chocolate and Boston cream donuts, but that eased over the year. Hawkins said she lost about 15 pounds and saw a reprieve from her hay fever.

Susan Roberts, a nutrition professor at Tufts University who oversees the study, stated in an e-mail that there are ''no medical issues yet [among the study's participants] and a lot of happy campers."

''I'm waiting for the results to see that it is safe," Roberts said, ''and then I'll probably join them." 

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