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December 24, 2004
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  Longer Life Mouse    

Long Life Gene - Scientists have found a gene that causes mice to live longer. (11/18/99)


"In Search of the Secrets of Aging" - National Institute on Aging

"Caloric Restriction in Primates: Will it work and how will we know?" - Journal of the American Geriatric Society, 1999

Dietary Guidelines for Americans, 2000

Roy Walford’s page

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What’s the secret to a long healthy life?

As this ScienCentral News video reports, some unusually long-living mice may have the answer.

Extending healthspan

Scientists have known since the 1930s that they can extend lifespan in laboratory mice and rats by restricting the animals’ diets. More recent studies have proven that caloric restriction also prolongs life in fruit flies, nematode worms, yeast and nonhuman primates. The goal of all this research, of course, is to learn how to increase human longevity.

"When we’re talking about delayed aging we are not talking about creating an increasing number of, you know, individuals with age-related problems, but we are talking about prevention of age-related problems," says Andrzej Bartke, professor and chair of physiology at Southern Illinois University School of Medicine. In a word, Bartke says, he wants to learn how to prolong "healthspan."

Bartke’s group wanted to know why Ames dwarf mice, whose dwarfism is caused by a mutation in just one gene, also live longer than their normal siblings. Both caloric restriction and the dwarfism mutation increased the prolonged healthspan in mice from an average of two years to an average of three, Bartke says. "If you put it in terms of human life, if the average lifespan in the human in industrial society is somewhere around 75, an increase of 50 percent would bring you to somewhere around 110 to 115."

To find out what would happen if dwarf mice were raised on a calorie-restricted diet, the group had to wait a long time—more than four years. Their results were reported in the November 22, 2001 issue of the journal Nature. (See graphic at right.)

Max healthspan

long life mouse graph
Normal mice on a normal diet (blue curve) live about two years. Normal mice on caloric restriction (green curve) start to age around the same time, but the slope is less steep. Their aging is slowed down. For dwarf mice (yellow curve), the curve is shifted to the right. They start aging later in life. Dwarf mice on caloric restriction (red curve) do both, and live longer by an added 25 percent.
image: Andrzej Bartke, Southern Illinois University

Bartke hopes to learn how the dwarf mice postpone aging. Doing so, he says, could help scientists figure out how to increase not just average healthspan, but also the maximum healthspan. "You can by some manipulations—for example in the human by diet and exercise—you can improve average lifespan by essentially preventing disease," says Bartke. "But you do not increase maximum lifespan usually, which means you are not postponing aging."

The group already has some clues. One of them is improved responsiveness to insulin. We humans commonly lose our insulin sensitivity as we age. In the extreme, we develop adult-onset diabetes. "These dwarf mice have low sugar and low insulin at the same time, this means that they respond to insulin better than a normal animal," Bartke says. "To put it in more practical human terms. This is an endocrine situation which is roughly opposite to type 2 diabetes." Bartke notes that diabetics can increase their insulin sensitivity using diet and exercise. "So this is something which even without the use of drugs can be achieved by a normal person by very accepted means."

Going hungry?

There are people who practice caloric restriction voluntarily, but there’s a big drawback: you go hungry. Bartke doesn’t recommend it, but the National Institute on Aging was sufficiently convinced by the piles of animal research to form a panel in 1999 to address the question of how it applies to humans. He says the Caloric Restriction Clinical Implications Advisory Group agreed that "at this point of our understanding of this intervention, what could be ethically recommended to people is to reduce your caloric intake to such an extent that you would not gain weight after your early twenties, after the age of 20 to 25. So that is probably a realistic goal."

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