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On The Fast Track

One man´s quest to lengthen life by cutting calories

Like an abstinent monk, Donald Laub, MD, takes an ascetic approach to the salad bar, passing up all the fat-laden concoctions for a handful of bare greens, three cherry tomatoes and a sprinkling of red cabbage, sprouts and jicama.

He tops off his tray with a bowl of clear chicken broth, with some green onions and a clump of broccoli thrown in for flavor. He savors the meager offerings on his plate very slowly, then pronounces himself satisfied with his lunch of less than 200 calories.

“I’ve had plenty. It was a nice meal,” he says with the contented look of a gourmand. For the past three years, Laub, former chief of plastic and reconstructive surgery at Stanford, has been religiously following a variant of the calorie-restriction diet that he believes will improve his health and may prolong his life. He’s already lost a significant amount of weight on the diet; his short frame, slightly stooped, has shrunk by 40 pounds, his pants sag around the waist and he’s had to punch new holes in his belt. But there’s a spark in his blue eyes, and he has ruddy cheeks that radiate the aura of good health.

Laub’s new diet is based on decades of research that has shown conclusively that calorie-deprived animals have better barometers of health and survive much longer than their well-fed counterparts.

But humans can’t possibly adhere to the kind of diets these caged, laboratory animals were subjected to. So Laub and his colleague, Louisiana plastic surgeon James Johnson, MD, have become strong proponents of a similar diet in which they eat freely one day, then consume near-starvation rations the next. Animal studies show this more-tolerable approach may confer some of the same benefits as daily calorie restriction.

“What I know I’ll get out of it is better health: less inflammation, less oxidative stress and better metabolic markers. That I know,” says Laub, 72, who also exercises daily and takes nutritional supplements. “What I’m hoping for is longevity of great proportion. Then we’d have to think of the social changes that will happen with that — because we’ll have a lot of extra people.”

The concept of calorie restriction as the key to longevity originated in 1935 with a published study by Cornell nutritionist Clive McCay, PhD, who showed that rats on vitamin-rich, but calorie-deficient diets lived significantly longer than their regularly fed counterparts.

Walter Bortz, MD, a gerontologist who has written several books on aging, remembers visiting McCay’s calorie-deprived rats as a youngster with his father, a physician who also focused on aging issues.

“They looked healthy. It was dazzling,” recalls Bortz, an adjunct professor of medicine at Stanford. “Their coats were smooth, their eyes were bright and they were even sexy — still procreating — when all the others were long dead. It has remained the most sturdy evidence about aging today.”

McCay’s work lay fallow for years, as few really took his studies to heart.

But the last decade has produced an explosion of research on calorie restriction, which has been shown in many organisms — from fruit flies, worms and spiders to dogs and, to some extent, primates — to be the only proven method for prolonging life. Though the evidence is scant in humans, the consensus among scientists is that calorie restriction could likely extend life in people, though there’s much debate about what might be the underlying mechanisms. And the actual practice of calorie restriction remains confined to a small band of devoted followers, for few can stomach the approach.

“Calorie restriction is NOT catching on in a big way in people because it is unpleasant,” says Leonard Guarente, PhD, a professor of biology at MIT whose work focuses on the mechanisms of aging.

Researchers surmise that an organism’s ability to thrive in the face of reduced energy intake evolved from earliest history, when neither man nor beast had the guarantee of a meal anytime soon. In the face of adversity, their DNA adapted through metabolic changes that enabled them to defend against the causes of aging, whatever they may be. Indeed, starvation was the standard human feeding pattern for millions of years, Bortz notes.

“It’s kind of like hibernation,” says Marc Hellerstein, MD, PhD, professor of human nutrition at the University of California-Berkeley and professor of endocrinology, metabolism and nutrition at UC-San Francisco. “When you have little to eat, your body goes into starvation mode, and somehow this extends your life. But it involves this unpleasant thing called starving.”

The first gene associated with calorie restriction and longevity was identified in brewer’s yeast in 1999 by Guarente and his MIT colleagues [see “Science of aging”]. They showed that the gene, whose counterpart in animals is known as SIRT1, becomes activated when animals are deprived of food, triggering a cascade of events that slow the aging process and help them survive.

Scientists are furiously at work trying to understand how SIRT1 works at the molecular level, for if they could somehow manipulate the proteins and pathways it regulates, they might be able to bottle a longevity pill. In the last six months alone, scientists have identified five proteins, operating through different mechanisms, that are thought to be key to the life-prolonging process, says Anne Brunet, PhD, assistant professor of genetics at Stanford. Through her work with tiny nematode worms, an organism commonly used in laboratory research, she’s identified one of these proteins, known as AMP-activated protein kinase, which is triggered when the animals are deprived of calories, helping them live longer.

Brush with death shakes up a life

Laub became interested in the topic of calorie restriction after he’d made an astonishing recovery from a malignant brain tumor that was diagnosed in 2000. The tumor was embedded in the blood vessels of his brain, making it particularly difficult to treat. His Stanford oncologist tearfully told him he had a 20 percent chance of recovery. “I was nearly dead,” Laub recalls. “Then I woke up like Rip Van Winkle. It was a miracle.”

He cherished life all the more and became determined to extend his as much as possible. Then one day in 2003, he got a call from a fellow surgeon and longtime collaborator in New Orleans, James Johnson, who was excited about a new study out of the National Institute on Aging in Baltimore. Mark Mattson, PhD, a neuroscientist and aging researcher, had reported that mice didn’t have to be continually deprived of food to live healthier and longer but actually did better if they starved only every other day. These every-other-day mice not only had low glucose and insulin levels, which are possible markers of longevity, but were more resistant to brain injury than those who were calorie-limited every day.

“It made me think about this in a whole different way,” Johnson says. “It was quite an inspiration to me and a lot of other people.”

“It’s easy enough to get through the down day if you manage it. You’re not starving.”

Other studies since have supported the value of an alternate-day dietary approach, with findings showing that it can lower the risk of diabetes, reduce blood pressure and cholesterol, improve the heart’s response to heart attack and prevent some forms of cancer, at least in laboratory animals. No one has shown that such a diet will yield the same benefits for humans.

Laub says he recognizes this dietary approach is a bit unorthodox, but then he’s not given to conventional ways of thinking or practice.

“I’m completely in the box as far as my professional associations are concerned,” he says. “But I’m out of the box in my ideas — very much. So it doesn’t bother me very much that nobody believes in it.”

In the 1970s, he became a pioneer in the field of sex-change surgery after he agreed to operate on a patient who had the face of a beautiful woman and the sex organs of a man. He ultimately performed the procedure on some 900 patients.

During that same period, when there were few plastic surgeons doing volunteer work in the Third World, Laub founded a nonprofit humanitarian group called Interplast, providing free reconstructive surgeries to children with cleft palates, disabling burns and hand injuries. The group’s volunteer physicians since have performed 64,000 surgeries for disadvantaged children in 16 countries.

Laub is no longer with the organization but recently started a new foundation, the eponymous DRL Foundation, in which he and Mexican physicians supervise medical residents performing free plastic surgeries for needy patients in Mexico.

But his major preoccupation nowadays is his new dietary approach, called the UpDayDownDay Diet, the subject of a forthcoming book he is co-authoring with Johnson. Under the diet, participants can eat freely one day, keeping good nutrition in mind, while restricting calories to between 20 and 50 percent of normal the next day.

Laub and Johnson, who both have performed liposuction on thousands of patients whose diets failed them, believe this is a dietary approach people can tolerate.

“You can’t look at the future as chronic daily deprivation,” Johnson says. “This frees you up to say every other day you can have what you want. We believe it works because it maintains people’s enthusiasm as they don’t look at a horizon of being deprived and hungry for the rest of their lives.”

Laub adheres strictly to the program, the first diet he’s ever been able to maintain, he says. On a typical “down” day, he gets up at 5:30 a.m. and eats nothing. By mid-morning, he’ll have a small glass of soy milk and a handful of nuts. Lunch often means a trip to the salad bar, where he “gorges on no calories” — vegetables that are nutrient-rich and calorie-sparse.

“It’s easy to get through the down day if you manage it,” he says. “You’re not starving. You’re dribbling in the calories.”

On his days of freedom, he eats sensibly: nutritious meals of rich vegetable soups, salads, a bit of meat, plenty of fruit and an occasional ice cream as a treat. “Before in my life, I never had a vegetable — ever,” Laub says. “I ate steak and potatoes, and I hated vegetables. Now I love all vegetables.”

For supplements, he takes a multivitamin and fish oil, as well as 1.5 grams of resveratrol, a compound found in red wine and peanuts that is believed to help extend the life span in many species. He also walks at least a mile a day in the hilly terrain of his neighborhood in Los Altos Hills, Calif.

Since he started the diet three years ago, Laub, who is 5-foot-9, has brought his weight down to 162. He says he’s never felt better, often getting a surge of energy on his “down” days. His wife, too, adopted the diet and says it made her feel more energetic. She stopped after a year because she was a slim person already and was concerned about her continuing weight loss, she says.

Laub theorizes the diet works to improve health by stimulating the SIRT1 gene, which stays turned on during the feast day. “It’s not a stress day,” he says, “but the gene system is still helping us.”

Though there’s no proof the diet works to improve health or longevity in people, Brunet, the Stanford geneticist, says the approach makes sense, particularly given the evidence in laboratory animals.

“I would say there is a reasonable chance it would increase life span,” she says. “I couldn’t see any reason why it wouldn’t work, though I would say humans are very different from mice.”

Laub acknowledges that it’s a big leap from mouse to man.

“Yes, there’s some faith involved when you make the jump in the question of longevity in humans — because there’s nobody who’s 120 or 140 years old who’s doing this,” he says. “Maybe I’ll be the poster boy.”

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Lunch with Laub

Donald Laub describes the diet he thinks might help prolong his life.





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