But Walford earned the most attention for his work and the potential of CR by using himself as a guinea pig. For 30 years, Walford subsisted on a daily diet of no more than 1,600 calories. The average American consumes roughly 2,500 calories per day, most from high-fat, processed foods.

By comparison, Walford's diet was decidedly Spartan. A typical breakfast consisted of a protein shake and banana; lunch was a vegetable salad; dinner a piece of fish or lean meat.

(Interestingly, Walford got a chance to observe how others fared on his CR diet in the 1990s while participating in the Biosphere 2 experiment. When plans to grow their own food went awry, the Biosphereans resorted to an extreme low-calorie diet that lasted almost two years. Walford later noted that despite significant weight loss, all eight participants remained in excellent health.)

The 5-foot-9 Walford weighed just 130 pounds. He told people his goal was to live to be 120 years old. He died earlier this year of amyotrophic lateral sclerosis, or Lou Gehrig's disease, an incurable neurological condition. He was 79, about five years older than the average American male's life expectancy.

Walford's death, however, has not dimmed enthusiasm for CR. It remains among the hottest subjects in longevity research. Since Walford's work, caloric restriction studies have been conducted – and are being conducted – on a wide variety of organisms, from yeast and spiders to fish and dogs. Most of these studies have reported significantly longer life spans in CR models.

More profoundly, writes Richard Weindruch, a geriatric researcher at the University of Wisconsin at Madison, caloric restriction appears to consistently increase not just the average life span of a subject population, but also the maximum life span or lifetime of the longest-surviving members of a group or species. In other words, CR seems to alter some basic process of aging.

Of course, studies of worms or flies reveal only so much. The big question is whether CR is effective in humans. Finding out is problematic, not least because people are already a relatively long-lived species. Getting significant data on whether CR extends human lives will take years, perhaps decades.

Nonetheless, the first controlled, large-scale studies of the effects of CR in humans have begun – a coordinated effort at the U.S. Department of Agriculture's Human Nutrition Research Center on Aging at Tufts University, the Pennington Biomedical Research Center in Baton Rouge and Washington University's School of Medicine in St. Louis.

In the meantime, researchers are plenty busy trying to figure exactly how CR boosts life span. Numerous theories have been proffered over the years. Among them:

CR slows the rate of cell division. In the 1960s, UC San Francisco gerontologist Leonard Hayflick discovered that cells, at least in the laboratory, appear to contain a finite number of divisions. After a cell divides 50 or so times, it dies. Researchers have speculated that CR slows cellular metabolism enough that those divisions occur less frequently, effectively slowing the cell's rate of aging. A reduced rate of cell division might also help explain why lab animals on low-calorie diets seem to suffer less from late-life cancers.

Contrarily, several studies have shown that, at least at the level of individual cells, CR may slightly boost metabolic rate.

"There is strong evidence that decreasing cellular metabolism is not involved in CR-induced life extension," said Edward Masoro, a professor of physiology at the University of Texas Health Science Center at San Antonio.

CR lowers glucose or sugar levels in the blood, reducing the accumulation of sugar on long-lived proteins, an effect that tends to disrupt cellular functions.

CR boosts immunological response and increases levels of protective hormones. Some scientists have noted that CR seems to work, in part, by alerting the body that food is scarce. The body responds by slowing its metabolism, boosting internal efficiencies, releasing energy stores in fat and upping the production of protective hormones that allow cells to withstand greater stress.

In roundworms, for example, starvation (or overcrowding) prompts the microscopic animals to slip into a kind of suspended animation, in effect shutting down until better times.

CR reduces mitochondrial damage. This view currently enjoys the greatest support, a fact not without some irony since the damage appears to be an unavoidable consequence of simply being alive. In every cell, there are tiny factories called mitochondria that convert raw fuel into usable energy. In the course of doing so, they produce molecules called free radicals as a by-product.

In modest numbers, free radicals are essential to carrying out necessary biochemical reactions. But they are highly reactive, oxidizing and destructive. Bruce Ames, a professor of biochemistry at UC Berkeley, estimates DNA in every cell in the human body experiences at least 100,000 "hits" or instances of free radical damage each day. Most of the time, the damage is quickly repaired. But mitochondria are particularly vulnerable to free radicals. They lack the protein shield of nuclear DNA and depend largely upon a single enzyme to make all repairs.

As people get older, their ability to internally fix free radical damage diminishes. Repairs go unmade; cellular injury piles up. Eventually, the theory goes, the accumulated, unfixed damage undermines a cell's ability to work efficiently, leaving it vulnerable to disease or death.

Less is more

Scientists at the Albert Einstein College of Medicine in New York have reported that calorie restricted rats had just one-fourth the body fat of their freely fed counterparts. That's significant because fat is not simply an inert, unsightly annoyance. It is an active substance that produces its own hormones and influences bodily functions. The fatter the rats, the researchers said, the harder it was for their bodies to efficiently metabolize sugar.

In addition, blood sugar levels were elevated and insulin sensitivity lowered – both factors linked to increased risk of diabetes.

A human study by John O. Holloszy, a professor of medicine at Washington University in St. Louis, published earlier this year noted that 18 people who had been practicing CR for three to 15 years showed dramatically reduced risk of developing diabetes or clogged arteries.

"It's very clear that calorie restriction has a powerful, protective effect against diseases associated with aging," Holloszy said. "We don't know how long each individual actually will end up living, but they certainly have a much longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes."

Meanwhile, Mark P. Mattson, a neuroscientist at the National Institute on Aging in Baltimore, has published several papers reporting improved brain protection in monkeys fed a reduced-calorie diet. He believes that CR prompts increased production of proteins and nerve growth factors that shield brain cells from harm. Other studies suggest that CR may elevate cellular resistance to diseases like Alzheimer's and reduce age-related deterioration of synapse transmissions in the hippocampus – a neural center for emotion and memory.

Never say diet

In laboratory studies, CR appears to be most effective when begun early in life. In mice, CR works best when begun just a few months after birth. Yet, some researchers have noted that CR seems to affect life span even when introduced much later. For example, Weindruch at the University of Wisconsin has noted that lab mice placed on a CR diet in early middle age lived 10 to 20 percent longer than control mice, and they suffered less frequent development of cancer.

Weindruch suggests consuming 10 to 25 percent less calories than an individual's personal set point – the genetically programmed body weight of a person. But finding that set point, he concedes, is difficult. Instead, dieters might try (with the assistance of a doctor or health adviser) to establish a calorie consumption level that reduces their blood glucose, cholesterol or other measure of health by a predetermined amount.

No one advocates CR for children, who require steady and substantial amounts of nutrients and calories to fuel growth and development. Christiaan Leeuwenburgh, director of the Biochemistry of Aging Laboratory at the University of Florida, doesn't recommend practicing CR until age 30 or older.

"Aging really becomes apparent after age 35 or 40," he said. "Younger people do well without CR in terms of repairing damage due to aging."

Caloric restriction may also pose problems for some women. Depending on the severity of the calorie reduction, resulting weight loss could affect fertility or increase the risk of osteoporosis or sarcopenia (muscle mass loss) in later life.

One proposed CR regimen recommends a daily intake of approximately one gram of protein and no more than half a gram of fat for every 2.2 pounds of current body weight. In other words, a 180-pound man should eat no more than 81.8 grams (3.2 ounces) of protein and 40.9 grams (1.6 ounces) of fat daily. A single Big Mac contains 25 grams of protein and 30 grams of fat.

Leeuwenburgh pursues a moderate form of CR, roughly limiting his daily intake to 2,000 calories. He says his diet is not extraordinary. It emphasizes chicken, fish, lots of vegetables and fruits and soy milk, but no red meat.

"And it's variable. I do a lot of strength training to maintain muscle mass. On days when I exercise hard, I eat more. On days when I don't, I eat less. I also believe in occasionally fasting, which gives the cells some feedback and stress that's helpful."

Indeed, regular fasting produces at least some of the benefits of CR. The National Institute on Aging found that the time between meals might be more important than their size. Specifically, lab mice kept on an every-other-day feeding schedule with no reduction in calories boasted reduced glucose and insulin levels similar to or better than mice on CR diets.

Pills, not meals

But some CR researchers have highlighted specific components as promising. In a paper published online last month in Nature, David Sinclair, an assistant professor of pathology at Harvard Medical School, reported that a chemical called resveratrol, found in red wine and some vegetables, triggers the same biological mechanisms as CR does in fruit flies and roundworms, lengthening the organisms' life spans an average of 20 percent without causing lethargy or infertility.

Sinclair reported similar findings last year in experiments with yeast.

A number of scientists have investigated 2-deoxy-D-glucose or 2DG, a compound that was first tested as an anti-cancer drug in the 1950s, but turns out to produce many of the classic responses of CR: reduced tumor growth, lower body temperature and higher levels of certain protective hormones.

Experiments suggest 2DG interferes with the way cells process glucose and their ability to manufacture internal fuel. As a result, scientists hypothesize, cells exposed to 2DG seem to downshift into a self-preserving, antiaging mode.

But 2DG's potential as an alternative to CR is practically nil. The compound has proven to be toxic at some doses in animals. Nonetheless, a full understanding of how 2DG works, say scientists, might lead them to equally effective but safer alternative compounds.

"If you look at all of the effects of CR, they're so complex that it's almost impossible to think that a single compound will have an effect. Maybe a cocktail, but I don't think there will ever be a magical pill," said Leeuwenburgh. "Genetic modification may be more promising."

At least eight genetic mutations have been discovered to reliably extend life in yeast, roundworms and mice. Indeed, many scientists have turned their focus toward identifying so-called "longevity genes," genes directly linked to significant aspects of aging, such as sugar metabolism, hormone signaling and cellular death.

For example, Lenny Guarante, a professor of biology at the Massachusetts Institute of Technology, and colleagues have determined that the Silent Information Regulator 2 gene, or SIR2, determines the life span of both yeast cells and roundworms. Add an extra copy of SIR2, the scientists found, and the organisms live longer than normal. Delete SIR2, and they die sooner than normal.

The SIR2 gene is not unique to yeast and roundworms. It is found in mammals, too. While there's no proof yet that SIR2 – or an analog – has a direct role in human longevity, the evidence seems to point that way, heightening hopes that genetic therapies may eventually be developed to either fight age-related diseases or slow the aging process itself.

But that's not going to happen soon, maybe not even in your lifetime.

Which leaves CR. If cutting calories by 30 percent sounds unappetizing, remember that even modest calorie reductions – Steven Austad at the University of Texas says 10 percent seems to be the effective minimum – can help.

According to the World Health Organization, there are more than 1 billion adults in the world who are overweight (28 percent of American men; 34 percent of American women). One-third of these billion people are considered obese.

Eating less certainly won't hurt them, and it may give them a few additional years to complain about what they're missing.