Analysis: Insulin-signaling longevity key?

BOSTON, July 20 (UPI) -- New research shows it may be possible to one day take a life-extending

pill that mimics the healthy effects of exercise and a low-calorie diet by lowering insulin signaling in the brain.

The key to a longer life is lower insulin levels, said Morris White,

a pediatrician and endocrinologist at Howard Hughes Medical Institute.

Less insulin helps cells fend off diseases that lead to an

early death, like cancer, said White, whose study appears in Thursday's

Science.

"With calorie restriction and exercise, cancer, diabetes, cardiac

disease and others all get postponed. It still happens, but at a later

age. It's thought to be at least partly involved in the longer life

span," White told United Press International.

Insulin is the substance made by the pancreas that allows cells to

metabolize glucose, and that diabetics need. But recent research shows that too much insulin is far from helpful, and instead makes cells vulnerable to diseases that may shorten life, like cancer, artery disease, Alzheimer's and Parkinson's disease.

While lowering insulin throughout the body can lead to a diabetic state, scientists found that allowing insulin levels to be high throughout most of the body, and lowering the insulin signaling only in the brain through genetic manipulation, extended the life of mice.

In White's study, the scientists manipulated genes in mice to produce 50

percent less insulin and saw the mice live 18 percent longer.

The same effect happens through exercise and eating 60 percent fewer

calories than normal, he said.

Although the mice were overweight, they lived longer and seemed active and youthful, White noted.

This result in particular seems to open the door to the possibility that

people can one day take a pill that will offer extra protection against

life-shortening diseases, White said.

``Maybe if we can decrease insulin signaling in the brain, then this

will be a very broad approach to reducing cancer and other diseases,

despite putting on weight. So you wouldn't have to go for a 60-percent

calorie restriction,'' White said.

"And you'd feel your life is longer because you wouldn't be miserable

from dieting," White added.

Some people who live past 100 may have a natural genetic tendency for

lower insulin signaling in the brain. They eat a normal amount

of calories or are even be a bit overweight, but still enjoy the benefit

of life extension, White said.

Research on diet, exercise, insulin and life extension has sped up

worldwide, and today many laboratories are doing this research, said

Makoto Kuro-o, assistant professor of pathology at University of

Texas Southwestern Medical Center.

Kuro-o discovered a protein in mice, dubbed Klotho, that controls

insulin and extends life. Klotho appears to be a different mechanism

from the genetic manipulation under way in White's laboratory.

"In the past several years there have been a lot of studies of insulin

in flies and worms. These studies probably gave us a very good clue to

applying the findings directly to mammals," Kuro-o told UPI.

"We actually don't know about brain function and what insulin is doing

in the brain. I think at least we are at the entry gate," Kuro-o said.