Study links insulin to weight and lifespan

Dieters have been given a little hope from a study that shows a change in a single gene in mice allows the animals to eat as much as they want while staying thin - and living longer into the bargain.

Many studies have shown that animals live longer when they eat, on average, about 30 per cent less than normal. The findings have led scientists to speculate that people, too, can extend their lives by dieting.

But no one quite understands why semi-starvation can help an animal live longer. Studies suggest it seems to have something to do with insulin and metabolism. One theory has been that if an animal eats less, the body produces fewer cell-damaging free radicals as a byproduct of metabolising food.

Dr C. Ronald Kahn of the Joslin Diabetes Centre at Harvard Medical School and colleagues genetically engineered a mouse that lacked a gene called fat-specific insulin receptor. This change limited the action of insulin on fat cells.

The mice, which they nicknamed Firko (for fat-specific insulin receptor knock-outs), fed freely without gaining much fat and also lived longer than normal mice.

They had 50 to 70 per cent less fat, no matter what they ate, and were less likely to develop diabetes than normal mice. They lived on average 134 days, or 18 per cent longer than normal mice. By the age of 30 months half the normal mice had died but 80 per cent of the Firko mice were still alive.

Writing in the journal Science, Dr Kahn and colleagues said their research suggests it might be something unique to fat that affects lifespan in animals.

"The concept that most people thought about is that free-radical damage might be coming from dietary toxins," he said.

Fat could be producing something that might be leading to free-radical damage.

People with type-1 diabetes, who do not produce insulin, will die without regular injections of the hormone. Dr Kahn said his mice survived well because their bodies block the action of insulin in just one place - the fat cells.

"Insulin has actions on many tissues - on glucose metabolism, liver, on muscle, even on the beta cells that make insulin," he said. The Firko mice still had all these functions.

Insulin's role in fat is to help fat storage. Dr Kahn believes that if his Firko mice were starved, they probably would not survive as well as normal mice, which have a life-saving layer of fat.

Scientists believe humans are prone to putting on extra fat because they evolved during times of starvation that winnowed out those who did not put on enough fat.

Dr Kahn believes it might be possible to design a drug that would have the same effect as turning off this gene.

"These pathways are very similar in people, and in terms of metabolism in general it has been very true that a lot of the lessons we learned from mice and rats and dogs have been pretty applicable to humans," he said.

"The question in humans is, could we produce a drug that would have these effects that would knock out insulin-signalling, but only in one tissue - fat. In theory this could be done."

He is looking for a biotechnology company or pharmaceutical specialist to work with to try to design such a drug. In the meantime, he also wants to study fat cells to see what it is they do that might affect lifespan.

- REUTERS

Herald feature: Health