Saturday, January 20, 2007

Restrict Your Calories To Live Longer

A Diet for the Immune System

As we age, so do our immune systems. It's why senior citizens are encouraged to get yearly flu shots. But researchers have found a way to keep the immune systems of monkeys young and healthy as they age by putting them on an extreme diet called "caloric restriction," which is the only proven way to dramatically extend lifespan in animals.

"Caloric restriction is probably one of the more spectacular biological manipulations," says Janko Nikolich-Zugich, an immunologist at Oregon Health and Science University. "It has been known for over 70 years now that it can extend life by about 30 percent.

And when we say caloric restriction we typically mean ... taking about a third fewer calories, or about 30 percent [of] calories, compared to what you would take if you had no dietary restriction at all. And ... not only do animals live longer under this treatment, but also they're much, much healthier. They don't seem to be showing many of the diseases characteristic of old age."

Monkeys were placed on a calorie-restricted diet at Oregon Health and Science University.
Previous research showed that caloric restriction also led to an improved immune response in rodents, so Nikolich-Zugich wanted to see if the same was true in "long-lived" animals like monkeys. So he and his team split a group of 42 monkeys into two groups—one on caloric restriction and one on a regular diet—for a period of three and a half years.

As they reported in Proceedings of the National Academy of Sciences, monkeys on caloric restriction had significantly stronger immune systems. They had more immune cells overall, and, most significantly, had more of a valuable type of immune cell called a naïve T cell. Most naïve T cells are created early in life. Once they get called into action to fight a specific pathogen, they turn into "memory T cells" that are only capable of fighting that specific pathogen. But naïve T cells are capable of attacking any pathogen, including ones the body has never encountered.

"As we use this naïve T cell reserve, we're less and less really prepared to fend off new pathogens," says Nikolich-Zugich. "And this is exactly one of the problems in old age. We don’t seem to be able to defend against some of the new pathogens that keep attacking us. And a typical case that you will see are the new strains of flu, where the elderly have serious problems combating them and we have [tens of thousands of deaths per year] due to flu related disease in the elderly population."

Janko Nikolich-Zugich and his colleagues found that monkeys on a calorie-restricted diet had more of a valuable type of immune cell.
Not only were there more of these kinds of cells in the caloric restriction group, but Nikolich-Zugich's team found the cells also seemed to function better. They introduced certain antibodies to the T cells in the laboratory (not in the animals themselves) and the T cells from the caloric restriction group proliferated and reacted much more vigorously.

Previous research by Nikolich-Zugich and H. Daniel Lacorazza, published in the Journal of Immunology suggested that aging reduces immune system function because the body starts producing more of a certain kind of T cell, called T cell clonal expansions, that are less effective in fighting disease. But he says it's possible that the bodies of the monkeys on caloric restriction were instead still making new naïve T cells.

"We could see a very dramatic improvement compared to what we normally see," says. "We could clearly show that caloric restriction had [a] very major impact on the makeup of the immune system and on its function, suggesting that one of the effects of caloric restriction on longevity might be through the improvement of the function of the immune system."

A "Drastic" Diet
While such a dramatic effect on health and aging may be alluring, Nikolich-Zugich stresses that the caloric restriction diet is probably too extreme for people, and potentially unsafe. There are people who are trying to adopt the diet into their lifestyle, but scientists have not yet tested the diet in people.

"People really should not jump on this treatment without careful consideration and knowing what it is," says Nikolich-Zugich. "The way a lot of [scientists] think about caloric restriction is that it represents a mild stress. It sort of represents like, taking a little bit of a poison and then you get used to it. And then you’re really, really good at tolerating large doses of stress. And that's a cautionary note; you might cross a threshold point where the organism is not able to react with this constructive adaptation to caloric restriction. You might instead actually really only show the detrimental side."

Instead, the point of his research is to understand how caloric restriction works at the molecular level. Knowing that might allow us to reap the benefits without enduring the diet.

"If we can understand which signaling pathways inside the cell are being stimulated or which might be inhibited, then you can use pharmacological intervention to really achieve much of the same effect," says Nikolich-Zugich. "If we can understand at the molecular levels what's happening then we should be able to devise treatments that would really not require necessarily for people to go on a fairly drastic diet…[and] trick [their bodies] into thinking that they’re on caloric restriction."

As to whether a more moderate diet might help our immune system, he says it's possible, but unproven.


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