Losing the Fat May Be Key to Longer Life

Lean mice live longer than their plumper kin, and now researchers may know why.

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By
HealthDay Reporter

FRIDAY, June 4, 2004 (HealthDayNews) -- Is there a connection between being lean and living longer? Researchers think there is -- at least, in mice.

It has been known for a long time that mice live longer on diets that severely restrict calories, but until now the reason has not been clear.

In new research, Massachusetts Institute of Technology (MIT) scientists experimenting with mice and mouse cells think they have found the answer.

Restricting calories causes a gene called SIR2 to become active, and this in turn activates another gene called PPAR-gamma that regulates fat storage.

When PPAR-gamma becomes active, fat is broken down and metabolizes, according to a new report in the June 3 online edition of Nature.

It has been known for about 75 years that, for mice, "a diet with very low calories seems to slow down aging and mitigate diseases of aging," said lead researcher Dr. Leonard Guarente, a professor of biology at MIT. "But what we haven't known is how that works."

The critical gene involved in the process is called Sirt1, which is the mouse form of the SIR2 gene found in humans, Guarente said.

This gene senses the scarcity of calories and causes fat storage cells to shed their fat. "The fat then gets pushed out of these cells into the blood where it gets metabolized," he explained. "This is a process that correlates with good health and longevity."

One of the reasons that mice on a calorie-restricted diet live longer is that they are incredibly lean, Guarente said. "And this is how they get lean."

Understanding the mechanism is the first step to developing drugs that mimic the effects of calorie restriction and deliver the benefits of calorie restriction, Guarente said. This has enormous potential in terms of diseases of aging.

I think that we can have drugs that can deliver some of the benefits of a low-calorie diet, without having to live a Spartan existence to get the benefit," Guarente said.

Dr. Heidi A. Tissenbaum, a gene expert at the University of Massachusetts Medical School, said this finding may be the mechanism that explains why calorie restriction works to extend life.

The finding is suggestive, but not conclusive, she added. "This could be one way SIR2 functions in calorie restriction, to extend lifespan," Tissenbaum said.

The broad implications could be new drug targets for treating human obesity and type 2 diabetes, she noted.

It may also lead to a new diet pill, she said. "The two things that work all the time are diet and exercise. I don't think that we will ever be able to take a pill and eat whatever we want," Tissenbaum said.

In terms of longevity, Tissenbaum said it's unclear how these genes act in later life.

"We don't know when these genes are active in the adult lifespan. We know how they act in the cell, but we don't know, until we have the data in mice and humans, that if you change one thing you can extend lifespan," Tissenbaum said.

Dr, Ronen Marmorstein, a researcher from the Wistar Institute at the University of Pennsylvania, added, "It is pretty clear that Sirt1 activity has an effect on fat metabolism and storage."

"Whether or not there is a longevity connection in mammals is still and open question," he added.

More information

The American Aging Association can tell you about growing older.

SOURCES: Leonard Guarente, Ph.D., professor, biology, Massachusetts Institute of Technology, Cambridge; Heidi A. Tissenbaum, Ph.D., assistant professor, program in gene function and expression, University of Massachusetts Medical School, Worcester; Ronen Marmorstein, Ph.D., researcher, Wistar Institute, University of Pennsylvania, Philadelphia; June 3, 2004, online edition, Nature

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