Biology of aging

06/02/04

Insulin plays central role in aging, Brown scientists discover

PROVIDENCE, R.I. -- When the chemical messages sent by an insulin-like hormone are reduced inside the fat cells of the fruit fly, the fly's lifespan increases significantly, according to new research conducted at Brown University.

A similar phenomenon has already been observed in worms, according to Brown biology professor Marc Tatar. But never before, Tatar says, has it been seen in fruit flies – whose 13,601 genes are shared in many ways by humans.

The experiment, detailed in the current issue of Nature, also sheds important light on the role insulin plays in the regulation of its own synthesis.

Block the hormone's action inside a few specific cells, the study shows, and the entire body stays healthier longer. Scientists previously thought insulin triggered other hormones to achieve this effect, but Tatar and his team found that insulin regulates its own production and that it directly regulates tissue aging. The principle: Keep insulin levels low and cells are stronger, staving off infection and age-related diseases such as cancer, dementia and stroke.

"Think of the body like a car," Tatar says. "We knew insulin controlled the car's speed by regulating things like the gas pedal and the fuel injectors. Now we know that insulin is also the fuel that makes the engine go."

To conduct the experiment, Tatar and four other Brown researchers created a line of genetically altered flies which had dFOXO – a protein controlled by the fly equivalent of insulin – inserted into the genetic material of fat cells near their brains.

Some flies were fed mifepristone, a chemical copy of progesterone. This hormone activated a switch attached to dFOXO, which in turn repressed the normal insulin signals inside the cells. As a surprising result, insulin production was lowered throughout the body. These flies lived an average of 50 days – 18 days longer than flies whose insulin signals went unchecked.

"We now know that insulin is a direct player in the aging process," Tatar says. "So the research fits some key puzzle pieces together. And it should change the way we think about aging."

Tatar's research is part of a growing body of evidence linking low insulin levels to increased longevity. In recent years, scientists have found that mice and other animals live longer when they eat a low-calorie diet, which reduces insulin production.

"Aging regulation is a complex physiological process of nutritional inputs, metabolic regulation and hormone secretion," Tatar says. "But we still have so many unanswered questions."

Tatar and his team conducted their research over an 18-month period. The work was funded by the National Institutes of Health, the American Federation of Aging Research, the Ellison Medical Foundation and Pfizer Inc.

Source: Eurekalert & others

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