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The monkey on the left is getting thirty percent less food, adn will probably live longer than the monkey on the right. But is it happier?
  The monkey on the left is getting thirty percent less food, adn will probably live longer than the monkey on the right. But is it happier?

Caloric restriction
By: Brahm Rosensweig, May 13, 1998
"Until you show me that you can postpone aging, I don't know that you've done anything," sniffs Michael R. Rose, geneticist at the University of California. "A lot of people can kill things off sooner, by screwing around with various mechanisms, but to me that's like killing mice with hammers -- it doesn't show that hammers are related to aging." Rose has indeed prolonged the lives of nematodes by selectively breeding them, and his comments paraphrase the new biology of aging where the name of the game is to alter animals' lifespans and them see why it happened. And so far, it seems to be easier to make them shorter than longer.
The oldest and most effective way to extend lifespan seems to be caloric restriction. This simple technique, which was first observed in the thirties, involves feeding animals a significantly lower quantity of calories than they would normally eat. A number of species have had the pleasure of living long hungry lives in caloric restriction experiments, including water fleas, fruit flies, single-celled protozoans, fish and rodents. Studies with rhesus monkeys are underway, but conducting studies with higher species is more difficult. Results seem to take a lifetime to come in.
Is it the reduction of calories that seems to work? It seems so. Diets reduced in fats, carbohydrates or proteins don't actually extend lifespans, nor do extra vitamins or any available antioxidant. But care is taken to create an extremely nutrient-packed diet. It's known as undernutrition without malnutrition
Click on the image below to visit the Biosphere 2.

Recently, the participants of the Biosphere 2 project were forced to eat a low calorie diet because their food production was less than projected. They experienced the same anti-aging indicators as the hungry monkeys. Click on the image above to see participant Dr. Roy Walford, a gerontologist, discuss his meagre fare from inside the Biodome.

Caloric restricted animals seem to "stay younger longer", exhibiting extended biologic youth and increased indicators for health, and decreased rates of disease. Markers of aging such as cholesterol and triglyceride levels are lower than all-you-can-eat animals. Insulin efficiency is up. THe growth of cancerous tumors slows down. Monkey that have been studied seem happy enough on their rations, though a bit anxious for their meals.
Is caloric restriction realistic for humans? We're talking about a 30 to 50 percent reduction of what you would normally eat, permanently. Dr David Gems, biologist at University College in London, doesn't think it would catch on. "Nobody would pay the price of an extended life span by spending their whole life in a state of starvation," he says. "In people, I would imagine it would induce lethargy and depression to live in such a way." Certainly, it's important to remember that animals that live their entire lives on caloric restriction are made into dwarves by their lack of food.

Thes little worms live longer if there's no food

The mechanism by which caloric restriction works is not well understood. Dr Gems work, which involves studying the DAF-2 gene in nematodes, may offer some insights. DAF-2 is a gene which makes a protein similar insulin-like growth factor (IGF) in humans and in other mammals. Mutations in the gene can increase life span by up to three times in nematodes.

"What it means, is that in the mutant the DAF-2 is defective, so in the normal animal the DAF-2 protein is actually shortening lifespan. If you take it away, then the animal's life span becomes longer," he explains. "There's a very good explanation as to what's going on, and to understand this you have to understand the biology of the worm. It has a peculiar double life cycle. When there's plenty of food around, the worms will develop very rapidly into the adult. If there isn't much food around, they will actually stops growing at the larval stage." Research suggests that though the adult worm only lives 18 days, the larva can remain in this state for up to 5 months.

Click on the image below to visit the lab of the long-lived nematodes on @discovery.ca

By altering a gene he dubbed the clock gene, Dr. Seigfried Hakimi has succeeded in extending nematode lifespans up to 8 times longer. Significantly, he found that the rate of activity that the worms showed was also slowed down - they moved slower, ate slower, etc. This finding points toward a connection between the energy economy of an organism, and its lifespan.

"They're sort of like a spore, in a way. They don't feed, they're relatively immobile. They sort of hang out, waiting for a change in the environment, and if food appears, then they'll actually continue developing into the adult. So what we think is going on is that the genome of the worm essentially has the information for two distinct life span programs.

There seems to be one mechanism in mammals that's similar -- caloric restriction. It's based on the fact that insulin is a metabolic regulator that's produced in response to dietary intake. Dr Gems points out that in the one mammalian mutation known where lifespan is increase, the Ames dwarf mouse, the pituitary gland is affected, which reduces the level of growth hormone. "Now, growth hormone acts via IGF-1, and the DAF-2 gene is homologous to the receptor for IGF-1," says Gems. "This is very speculative, but there's all these tantalizing parallels."

But he reiterates that dietary restriction is not the goal. "It might be possible conceivably," he speculates, "if the DAF-2 pathway were actually involved in the caloric restriction, to design some drugs that would switch off some part of a pathway. That might induce whatever it is that happens during caloric restriction in such a way that one didn't have to suffer this sort of dietary restriction."

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July 24, 2001
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