Until this study, scientists understood controlled famine extended the life of those leaner mammals by as much as 50 percent. Moreover, those mammals didn’t suffer from the diseases connected with old age.

How can they do that?

Typically, a mammal burns proteins and carbohydrates in its food immediately and stores fat in white adipose tissue. When its caloric intake is reduced, this tissue stops storing fat and releases it to be metabolized. When fat is released or metabolized by the body, scientists learned the Sirt1 protein senses a state of short-term famine and shuts off the receptors that keep fat stored in cells.

When food is less plentiful, the Sirt1 protein represses and binds to genes controlled by PPAR-gamma, the body’s fat regulator, preventing the body from storing fat.

So far, the Sirt1 protein has been found to work in mice. If this protein works the same way in humans, researchers theorized it could help people not only live longer but avoid the disabling array of diseases associated with aging, including diabetes, cancer and heart disease. What do researchers hope for? For one, white adipose tissue also creates hormones. Researchers believe the placement of those hormones in the bloodstream could "tell" the body how quickly to age. Additionally, if a drug could be made to bind with Sirt1 that fools the body into releasing fat, humans could enjoy the benefit of calorie reduction without side effects.

In a related study involving fruit flies, when chemical messages sent by an insulin-like hormone are reduced inside fat cells, the lifespan of the fly lengthens greatly.

Although this reaction has been previously documented in worms, this discovery opens new possibilities. Why? Fruit flies have some 13,000 genes that are shared in many ways by humans.

Research also uncovered information about the role insulin plays in regulating its own production. The study found by blocking the insulin hormone inside a targeted number of cells, the body stays healthier for a longer time.

Scientists once believed insulin worked by triggering other hormones to achieve this effect. This new study showed, however, insulin regulates its own production as well as tissue aging. The good news: By keeping insulin levels low, cells get stronger, allowing people to better hold off infections and age-related diseases like stroke, dementia and cancer.

Researchers created a line of genetically altered flies with dFOXO, a protein controlled by the equivalent of insulin in a fly, placed in fat cells near their brains. Some flies were given mifepristone, a progesterone copy. This hormone activated a switch attached to the protein that repressed normal insulin signals in cells.

Insulin production dropped and, surprisingly, test flies lived more than 50 percent longer than those whose insulin levels were unchecked.

Nature June 2, 2004

EurekAlert June 2, 2004