Insulin sensitivity and long life

... Scientists have known since the 1930s that yeast and many animal species live 30 to 50 percent longer when they are fed a spartan diet, containing about one-third fewer calories than normal. One frequently observed effect of this extreme diet is an improved sensitivity to insulin. This sensitivity causes the body to produce less of the hormone. At the other extreme, people with type 2 diabetes have poor insulin sensitivity, so their bodies ramp up insulin production to compensate.

Blackwell and his colleagues studied how insulin regulates a protein called SKN-1 in roundworms. This protein orchestrates a family of detoxification enzymes that protect cells by removing free radicals--vandals of the cellular world that can shorten life span. The team found that insulin decreases the activity of SKN-1, throttling down these detoxification enzymes and leaving cells less protected.

Boosting SKN-1 levels by adding extra copies of the gene for SKN-1 extended the worms' life spans by 25 to 30 percent, the researchers report in the March 21 Cell.

"The fact that having more SKN-1 around is sufficient to extend life span is a very important result," comments Matt Kaeberlein, a longevity researcher at the University of Washington in Seattle. "That's proof that SKN-1 is really involved in aging."

A study published last year in Nature did show that SKN-1 within nerve cells in roundworms' heads is essential for the life-extending effects of calorie restriction (SN: 6/30/07, p.414), but the new study shows a variant of the protein in the gut influences aging in a different way--one that's controlled by insulin.

One explanation for why insulin appears to shorten an animal's life span could be that insulin requires an oxidizing chemical environment--friendly to free radicals--to do its primary function of regulating blood sugar. To disarm free radicals, the detoxification enzymes create the opposite environment, a reducing one. So the body might be trading a bit of cellular damage for the sake of improving insulin's ability to do its job, Blackwell suggests. - findarticles