HEALTH HORIZONS : NUTRITION : Eat Less, Live Longer : A LIFE SPAN OF 140 YEARS--OR MORE? THE WAY TO REACH THIS POTENTIAL FOUNTAIN OF YOUTH IS WITH FOOD--MUCH LESS OF IT.

The days of our years are threescore and 10; and if by reason of strength they be fourscore years, yet is their strength, labor and sorrow; for it is soon cut off, and we fly away.

--Psalms 90:10

Until quite recently, the above 2,500-year-old biblical reference to a life span of 70 years--80 with “strength, labor and sorrow”--concurred with the vision and reality of modern science. Few of us make it to 90, after all, and fewer still to 100. Many of us look around and believe, as did Robert Lewis Stevenson, that “by the time a man gets well into the 70s, his continued existence is a mere miracle.”

Now a few scientists are challenging that assumption. A life span of 140 years? Or longer? It could be possible, they say, if experiments they’ve done with rodents for the past 20 years can be extrapolated to humans. The way to reach this potential fountain of youth is with food--much less of it.

Dr. Roy Walford, a research gerontologist at UCLA School of Medicine, has nearly doubled the life span of laboratory mice and notably extended their reproductive lives with a regimen called caloric restriction, which cuts their calorie intake to just half of what they’d consume with their regular diet. It’s hard to say whether these mice are happier than mice that are allowed to eat whatever they want, but they are smaller, livelier and healthier-looking.

It is virtually impossible to find mice that are more than 2 1/2 years old in any lab or in nature--except at UCLA and the few other laboratories working on calorie-restricted diets, where chipper, active mice live to be more than 4. They’re the Methuselahs of rodents.

Caloric restriction appears to extend the life of a large number of animals besides mice, Walford says. It has worked with fish, protozoa, nematodes, spiders and mollusks. Preliminary work at the National Institute on Aging and at the University of Wisconsin at Madison indicates that caloric restriction also may extend life in primates--strong evidence that further exploration of human longevity may well be worth scientists’ time.

While Walford waits for approval to try the regimen on humans, he is trying it out on a human guinea pig--himself. After several years of eating about 30% to 40% fewer calories than the average American of his height--he consumes between 1,500 and 2,000 calories a day--Walford reports he’s feeling just fine. The 66-year-old scientist has lost 20 pounds during his experiment and now carries 140 pounds on his 5-foot-8-inch frame. Indeed, his spare mien and his penchant for informal garb make him look like more of an aesthete than he really is, he says. His weight loss has leveled, and he has no trouble maintaining his 140 pounds.

“I’m eating enough to keep my machine going,” Walford says. “About a third of the journalistic literature has me as kind of a starving saint in the desert.”

He also complains that reporters call his regimen a “starvation diet.”

“It definitely is not a starvation diet,” he says, adding that starvation is defined as a 60% reduction in calories over a period of time.

Walford’s calorie-restriction program involves not only reducing the number of calories he consumes but also being selective about what kind of calories they are. Although many scientists doubt that Walford’s diet will extend his life--or that of any other human--they can’t help but notice that what he eats greatly resembles the diet that’s recommended for fighting heart disease. He’s simply cut the quantities by about a third. Walford’s meals consist of lots of fish, fruit and vegetables, and he has cut his red meat consumption considerably. He drinks alcoholic beverages only occasionally. This diet, he says, can’t hurt. And, he believes, this shrunken version of a health-food diet might not only save lives but extend them.

How could eating smaller amounts of better food act to slow aging? Walford believes that such a diet modification keeps the immune system from breaking down. That breakdown, he theorizes, causes aging. In the early 1970s, he discovered the work of Clive McCay of Cornell, who three decades earlier had been the first to advance the idea that restricting calorie intake could lead to longer life. If McCay was right, and if his own theory was correct, Walford believed, tests on the immune systems of animals with restricted diets would reveal signs of delayed senescence. And that, he says, is what he has found in his studies of mice.

Walford has six rooms full of mice in the basement of the public health building at the UCLA Medical Center. Those animals have only two functions in life, says Steven Harris, Walford’s assistant, who runs the experiments: They eat, and they die when their time comes. What they eat and when they die is the crux of the experiment. Each mouse has its own cage, the floor covered with clean sawdust. Harris splits the mice into two groups: control animals, which are allowed to eat as much as they want, and those with restricted diets. Walford forces mice in the second group to eat everything they’re fed and thus provide a base line for the experiment.

All the mice get specially formulated food fortified with vitamins, minerals and protein. A third of mice on restricted diets get 20% less of the amount fed the control group. Another third get 40% less, and the remaining third get only half what the control mice eat.

The results are unambiguous. The maximum life span of the least restricted eaters is 36 months. “If you restrict them a little bit, 20%, the maximum life span goes up to 42 months,” Harris says. “If you restrict them to 50% of what they’d like to eat, then maximum life span goes up to 52 months. If you restrict them by 40%, it goes clear out to 54 months.” Thus a 40% reduction results in maximum longevity. “Average life span goes from 27 months with the animals eating all they want to 54 months on the maximum amount of restriction,” Harris says.

“This needs to be seen in perspective,” he adds. “Human beings in this country have a life expectancy of something like 74 years for men and 79 for women. If you were to cure all cancer tomorrow, life span would increase by three years. If you were to cure all heart disease, you would get another three years, maybe 3 1/2. That’s less than 10%.”

In the experiments, “we’re talking (about) 80% to 90% increases,” Harris says. The experiment has been replicated enough that its findings are generally accepted for mice. Scientists are so sure caloric restriction slows aging that it is being used as a tool for studying the aging process.

But when Walford and others extrapolate those findings to human longevity the issue gets controversial. One skeptic, Edward Masoro of the University of Texas Health Sciences Center in San Antonio, thinks that if caloric restriction really did work on humans, there would by now have been people who had accidentally stumbled onto a restricted diet and lived to be 140--which hasn’t happened as far as anyone knows. But some humans do live that way, Walford says. The people of Okinawa eat a Japanese-style diet of fish and vegetables but consume 40% fewer calories than the Japanese do and even fewer than Walford does. Far more of them live to be 100 than do people on other Japanese islands.

Anorexics, soon after diagnosis and just before they reach starvation levels, are “quite healthy,” Walford says. “Their immune response is better, they are resistant to infection and they have a great deal of energy.”

How onerous you find Walford’s diet depends on what you’re used to, Harris says. “For native Japanese, it’s not very onerous at all because they are used to a very low-fat, high-complex-carbohydrate diet with fruits and steamed vegetables. For the average American who’s used to Big Macs and hot dogs, ice cream and whole eggs, it’s tough.”

One key to making the diet successful, Walford found, is to lower the caloric intake gradually. When scientists suddenly put previously unrestricted mice on highly restrictive diets, the mice seemed to go into shock.

Generally, Harris and Walford have found that younger mice respond better than older ones. “It makes a difference if you start rats and mice at one year of age,” Harris says. “If you start at two years of age, . . . it’s not clear that it makes a big difference.” The equivalent in humans is to begin the diet at age 30, he says, when it has a much greater chance of succeeding, than at age 60.

Several research groups have begun tests on primates, the usual step before starting human testing. One group, at the National Institute on Aging’s Gerontology Research Center in Baltimore, is working with juvenile and adult male rhesus and squirrel monkeys to determine the effects of dietary restrictions on the animals over the next few years.

Donald Ingram, one of the researchers, says that by measuring certain markers in the blood of the animals, the scientists will be able to follow changes in the monkeys’ bodies as the animals get older. The monkeys also were divided into control and restricted groups, with the restricted monkeys getting 30% fewer calories than the control group for three months. The scientists are beginning to record preliminary and promising results, but all they can say now is that the restricted diets do not appear to be harmful.

Richard Weindruch, working with William Ershler and Joseph Kemnitz at the University of Wisconsin, has been working with 30 male rhesus monkeys for more than a year. Half are control animals; the other 15 are on restricted diets of 30% fewer calories. Weindruch says that after one year there are signs that aging is slowing down in the latter group, that the ratio of insulin to glucose is more “youthful” in the monkeys on the restricted diet. The same kind of chemical effect has been seen in calorie-restricted mice, he says. More animals--including females to show the effects on fertility--will be added to the study, Weindruch says.

But it will be difficult to test the diet on humans, Harris says, and that makes scientists reluctant to try. They must know exactly what the subjects eat, meaning they have to be monitored constantly. That’s not impossible in short-term studies involving diet. Then subjects can be locked away from the outside world so that everything they eat can be measured, and so that the food contains chemical markers to indicate whether anyone is cheating.

But a 50-year study--and researchers contend an experiment into human longevity would have to be that long to ensure accuracy--would be daunting. No one wants to be locked away for half a century. Scientists are also holding back because working on human mortality is intrinsically controversial.

“This whole subject is kind of taboo,” Walford says. “Mankind has had problems thinking about death, and has different ways of not thinking about it, like religion, philosophy. This comes over to medical professionals too. They don’t want to touch anything that has to do with aging unless it’s 100% proven. If you look at a general view of medicine, about 50% of (treatment) that’s prescribed is not proven, it’s a consensus.”

Another problem impeding human experimentation is that no one knows how dietary restriction works in slowing aging. Walford thinks it prevents the natural autoimmune response of senescence, in which the body begins destroying its own tissue, and increases the ability of the DNA in the cells to repair itself. He says he has biochemical evidence to support that view.

Eating less also might trigger an evolutionary survival response. “During a food shortage, animals shift their energy from growth, reproduction and basal cell reproduction to defensive repair, thus enabling them to survive a time of shortage, Walford says. Faced with a cutback in food, the animals’ bodies might go into that defensive mode, repairing the wear and tear of aging much more efficiently than usual.

All this leads to one question: If humans are not programmed to live only the biblical “threescore and 10,” how long can we live if aging is “cured”?

“Put it this way,” Walford says, conceding that he’s guessing. “If we do away with all causes of disease and stop the aging process, and the only thing left is accident, and accidents remain at the present rate, which is 5% of deaths, then our (average) life span is 600 years. Lower the accident rate,” he says, “and you live longer.”

Then the time of humanity might be 30 score and 10. But would it just seem longer?