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Although this news is a bit old, it's very relavent to YBMers.  So here you are!

A small sign on the cage of Ludwig, an older but fit-looking rhesus monkey, warns "caution, grabby."

Understandably, Ludwig reaches out of his cage a lot. He's been on an extremely low-calorie, experimental diet for years and he probably would eat anything he could get his hands on.

At the same time, Ludwig's handlers are hoping to get a better grasp of a quickly evolving concept that could prove to be a mini fountain of youth.

Can humans live to beyond 100 if they eat a nutritionally packed diet that contains about 30 percent fewer calories than normal?

Studies in a variety of animals, including fish, rodents and dogs, have consistently showed a 25 percent to 50 percent increase in life span from calorie restriction.

But it's likely to be years, perhaps decades, before a longevity benefit can be proven with human experiments.

For that reason, the monkey experiment at the Wisconsin National Primate Research Center is being watched closely by scientists around the world. People and rhesus monkeys share 93 percent of the same genes.

Even though the study, which began in 1989, is likely to go on for years, early health benefits seem to be emerging.

And in the last few months, some of the first, short-term human experiments also have yielded tantalizing results, making the Madison experiment all the more important.

The studies are giving more credence to the concept that only had been tested in animals.

Earlier this month, a group of researchers found that depriving overweight, but non-obese, people of about 25 percent of their normal calories, while still having them eat nutritionally balanced diets, led to physiological changes associated with increased longevity.

The six-month study involving 48 people showed that calorie restriction led to improvements in insulin levels, a beneficial decrease of about one degree in body temperature and less DNA damage to cells.

The study also found similar benefits in a group whose members cut their calories by 12.5 percent and exercised enough to burn 12.5 percent of their caloric intake.

That's an important finding because while restricted diets are considered too difficult to maintain for the vast majority of people, exercise is an attainable goal. Exercise also can help preserve muscle.

Those who exercised their way into a caloric deficit did so by riding stationary bikes or running on treadmills, said co-author Steven Smith, an associate professor of endocrinology at the Pennington Biomedical Research Center in Baton Rouge, La.

"They worked very hard," Smith said. "It wasn't just walking around the block."

The authors said the exercise finding suggests that the driving force behind the phenomenon is energy deficit rather than just cutting calories.

The research, which was published in the Journal of the American Medical Association, comes on the heels of a separate study showing that a small group of people on similar restricted diets had younger hearts and less inflammation in their bodies.

The study compared 25 people who had been on restricted diets (between 1,400 and 2,000 calories a day) for an average of six years to 25 similar individuals who ate typical Western diets (2,000 to 3,000 calories).

Ultrasound tests showed the hearts of those on the restricted diets were more elastic _ the heart normally stiffens with age.

"Their hearts looked like someone who was 15 years younger," said Timothy Meyer, a member of the Washington University team that reported the finding in January in the Journal of the American College of Cardiology.

They also had substantially lower levels of inflammatory substances in their blood, proteins that are associated with increased risk of heart attacks and strokes.

While the finding does not guarantee they will live to 100, their life expectancy is higher, said co-author Luigi Fontana, an assistant professor of medicine at Washington University in St. Louis and the Italian National Institute of Health.

"Their risk of developing a myocardial infarction (heart attack) or stroke was close to zero," Fontana said.

There are a number of theories about what is behind the health benefits of a restricted, but nutritionally packed diet.

Fontana said much of the effect may come from reducing the chronic state of inflammation that exists when there is too much fat in the body.

Far from being inert, fat cells secrete hormones and other proteins known as cytokines, which can lead to inflammation and the stiffening of various tissues, such as blood vessels and heart muscle.

Eliminating excess fat can dramatically reduce that process.

Caloric restriction also induces a different metabolic state that may retard the aging process, said Richard Weindruch, a professor of medicine at the University of Wisconsin-Madison.

When cells make energy, unstable oxygen atoms known as free radicals are produced. Free radicals can damage DNA, which, in turn, can lead to diseases such as cancer, coronary artery disease, Type 2 diabetes and Alzheimer's.

Weindruch has used a new gene chip technology to analyze vast arrays of genes in animals on restricted diets. He has found that caloric restriction beneficially affects a variety of genes in ways that retard the aging process.

His company, LifeGen Technologies, now is using that technology to screen various nutritional combinations to see if those foods and various anti-oxidants and other micronutrients can mimic the effects of caloric restriction.

Given the difficulty of maintaining a restricted diet, finding foods or drugs that mimic caloric restriction is one of the ways the phenomenon eventually may be applied to a large number of people, said Weindruch, who also works as a geriatrics researcher at the VA Hospital in Madison, Wis.

Of course, another possibility would be the development of a safe diet drug that allowed people to cut calories by 25 percent over a period of years.

"If that happens, hundreds of thousands to millions of people could restrict their diet long term," he said.

Researchers at Tufts University now are trying to produce the optimal regimen that minimizes hunger and allows more people in studies to adhere to their diet, said Susan Roberts, a professor of nutrition and psychiatry at Tufts.

They are using a diet that maintains normal protein levels as well as vitamins and minerals and cuts calories from fat and carbohydrate, she said.

So far, the most successful regimen has been in a group of people that have been able to cut calories by 17 percent for one year, she said.

In addition to dealing with hunger, people on restricted diets, especially those who cut calories 30 percent to 40 percent, may experience a range of often unwanted side effects. Those include low blood pressure, reduced sex drive, menstrual irregularities, infertility, bone thinning, cold sensitivity, loss of strength, slower wound healing and various psychological conditions, according to a recent review article in the journal Mechanisms of Ageing and Development.

"Because the long-term effects of CR (caloric restriction) in humans are not yet known, precautions should be taken before engaging in such a severe CR regimen," the article concluded.

Of course, Ludwig and the rest of the monkeys in the study at the Primate Research Center don't have any choice in the matter.

They get either a normal amount of monkey food or 30 percent less than normal.

The study started with 76 monkeys, 38 in each group. The monkeys are kept together in rooms in individual cages.

It's apparent upon entering the high-security lab which monkeys are in which group.

The food trays of the restricted monkeys are always empty while various amounts of food remains uneaten in the trays of the non-restricted monkeys.

Upon closer inspection, there's another apparent difference: the restricted monkeys generally look younger. They have fewer wrinkles and less aging in their faces, their coats look healthier and they are trimmer.

In addition, four of the monkeys in the non-restricted group developed insulin-dependent Type 2 diabetes, compared with none of the restricted monkeys, said Ricki Colman, associate scientist at the center.

There also appears to be less osteoarthritis in the restricted monkeys, she said.

More importantly, Colman said, "We are starting to approach differences in survival."

There have been eight aging-related deaths from ailments, including cancer, heart disease and diabetes in the non-restricted group vs. four such deaths among the restricted monkeys, she said.

A total of 52 monkeys remain in the study. Since the average life span of a rhesus monkey is about 27 years, it's likely to be another 15 years before the experiment is final, she said.

"I think we need to go until the last animal is standing," Colman said.

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