Weight Loss :: Connection between being lean and living longer

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

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.”

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.

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. This could be one way SIR2 functions in calorie restriction, to extend lifespan.

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

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.

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