Antidepressant lengthens worm's life

An antidepressant may help worms live longer by tricking the brain into thinking the body is starving, U.S. researchers reported on Wednesday.

The drug, called mianserin, extended the life span of the nematode Caenorhabditis elegans by about 30 percent, the researchers reported in the journal Nature. They hope to find out if the same mechanism can help people live longer.

Three other compounds, including another antidepressant, have similar effects, said Michael Petrascheck of the Fred Hutchinson Cancer Research Center in Seattle. But the life-extending benefits come at a cost.

"Weight gain and increased appetite seems to be one of the side effects. It is one of the reasons these are not such popular antidepressants," Petrascheck said in a telephone interview.

Many studies have shown that slightly starving certain animals - reducing how much they eat by about 30 percent - can cause them to live longer.

It is not entirely clear if this occurs in humans, but researchers are keen to duplicate the beneficial effects of calorie restriction without the misery of going hungry.

Howard Hughes Medical Institute researcher Linda Buck and colleagues were looking for drugs that might do this.

C. elegans is a nematode, or roundworm, much studied because despite its tiny size, it has biologic similarities to humans and other animals.

Buck's team did a random search through 88,000 different drug compounds to see if any of them happened to make C. elegans live longer.

They found four drugs that extended life span by 20 percent to 30 percent. The drug with the strongest effect was mianserin, in a class of drugs known as tetracyclic antidepressants.

It blocks brain cell signaling by the neurotransmitter or message-carrying chemical serotonin, which is linked with mood and appetite.

The drug is used in Europe under several brand names, including Bolvidon, Norval and Tolvon. Its side effects include aplastic anemia and other effects on immune system cells.

Buck's team found that in addition to interfering with serotonin in the worm, it also blocked receptors for another neurotransmitter, octopamine.

They said some other research suggests that serotonin and octopamine may complement one another - with serotonin signaling the presence of food and octopamine signaling starvation.

Buck said it is possible that mianserin drug tips the balance in the direction of octopamine, tricking the brain into thinking it has been starved.

Petrascheck said another antidepressant, mirtazapine, had similar effects. An antihistamine and migraine drug called cyproheptadine, as well as a compound not used in people called methiothepin also affected serotonin and extended worm life span.