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5-Animals: GE mice live longer and remain leaner

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TITLE:  Study in mice shows drugs combating obesity, lengthening life
SOURCE: The Boston Globe, USA, by Alice Dembner
DATE:   Jan 24, 2003

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Study in mice shows drugs combating obesity, lengthening life
Altering metabolism could reduce need for calorie-cutting

Scientists in Boston have developed genetically altered mice that remain
lean no matter how much they eat and live nearly 20 percent longer than
normal - leading doctors to suggest the study could provide a path to new
drugs to cut obesity and extend human lifespan.

The researchers at the Joslin Diabetes Center restricted the mice's
ability to store fat by eliminating their insulin fat receptors. Then,
they allowed the mice to eat normally. The mice remained healthy,
avoiding diabetes, but weighed up to 25 percent less than other mice and
had up to 70 percent less body fat. On average, they lived 18 percent -
134 days - longer than other mice.

"If we could find a drug that would have this effect in people, it would
be a valid approach for obesity," said Dr. C. Ronald Kahn, the lead
researcher and a professor of medicine at Harvard Medical School. "There
are a number of companies working on ways to influence body weight
without affecting appetite. Within a five- to 10-year period, we will
begin to find some effective drugs from this line of research."

That would be welcome news for nearly 60 million Americans who are obese.
The federal Centers for Disease Control and Prevention recently estimated
that 47 million people have medical problems associated with obesity.

The study in mice, published today in Science, was designed to help
explain why all kinds of animals, including humans, live longer if the
amount they eat is reduced by 15 to 30 percent. Some researchers have
hypothesized that eating less may decrease metabolism and the production
of damaging materials known as "free radicals" in the body. Most thought
that restricting calories was more important than staying lean. But the
new research suggests that the leanness is more important, and can be
achieved through insulin regulation and increased fat metabolism rather
than simply reducing food intake.

"This makes us rethink our hypotheses about what causes longevity," said
Dr. Andrew Greenberg, a researcher at the Tufts Human Nutrition Research
Center on Aging. Among the other known factors are genetics and the

Other researchers at Tufts are beginning a study on human volunteers to
look at the effects on lifespan of cutting calories dramatically. But,
for most people, cutting calories by up to 30 percent is an unappealing
option. So scientists and drug companies have been looking for other means.

Focusing on the metabolism of fat is one avenue. Other researchers are
looking at growth factors and genetic modifications. A local biotech
company, Elixir Pharmaceuticals, has been pursuing several of these tracks.

But applying animal research to people is always tricky, even though mice
are seen as good models for human studies of obesity and longevity.

Kahn said cancer drugs have already been developed that block insulin
receptors in all kinds of body tissue. The task, if the current work
progresses, would be to find a drug that would only work on fat tissue.
"It's not easy, but it should be theoretically possible to do this," said

Leonard Guarente, an MIT biology professor who is working with Elixir and
recently published a book called "Ageless Quest," said:

Kahn's work "sets the compass in the right direction. It underscores the
relationship between lean body mass and aging, which is emerging as a
theme in aging research.

"If we can boost the metabolism of fat, that in itself might extend the
lifespan," Guarente said. "In addition, there could be important
implications for treating diabetes and obesity."