Antidepressant lengthens worms’ lives

“An antidepressant drug lengthens tiny worms' lives and offers hope of humans living longer too” BBC News reported today.

The Daily Telegraph also covered the story, saying that the antidepressant mianserin increased the lifespan of nematode worms, and enabled them to reach “the equivalent of 100 human years”. The news stories suggest that the drug extends lifespan by mimicking the effect of “virtual starvation”, which is known to increase the longevity of worms and also other species including mammals.

BBC News reported that “experts said the findings might point to there being genes in humans that could be targeted to increase lifespan”, although this interpretation was made by only one of the researchers it interviewed.

This story is based on a laboratory study in the microscopic worm Caenorhabditis elegans , which scientists often study in longevity experiments. Although the results of this research are of good quality, they do not necessarily mean that mianserin will have the same effect on humans who are somewhat more complex organisms.

Although BBC News reports that a human gene could be targeted to control lifespan, this is speculation rather than rigorous interpretation of the study.

Where did the story come from?

Dr Michael Petrascheck and colleagues from the Fred Hutchinson Cancer Research Center in Washington carried out this research. The study was funded by the Howard Hughes Medical Institute and the Ellison Medical Foundation and was published in the peer-reviewed scientific journal: Nature.

What kind of scientific study was this?

This was a laboratory study looking for chemicals that can increase the lifespan of the microscopic worm Caenorhabditis elegans . This worm normally has a lifespan of about three weeks.

The researchers tested 88,000 different chemicals to see if they would extend the lifespan of the worms. They did this by adding the chemicals to the liquid in which adult worms were growing, and comparing how long they lived compared to worms that were not exposed to any chemicals.

When the researchers identified chemicals that increased the lifespan of the worms, they conducted further experiments to look at whether similar chemicals had the same effect. They were also interested in establishing why the chemicals had this effect on the worms by seeing if they had the same effect on worms with genetic mutations in various chemical pathways. Some of these mutations were already known to extend the lifespan of the worms.

What were the results of the study?

The researchers identified 115 chemicals that increased the worms’ lifespan. The chemical that increased lifespan the most (by 20%) was similar to several antidepressant drugs. The researchers then tested similar chemicals, and found that two drugs used as antidepressants in humans, mianserin and mirtazapine, increased worm lifespan by 20 to 30%. Other types of antidepressants, such as the selective serotonin reuptake inhibitors - the most commonly prescribed form of antidepressants - did not increase lifespan.

Mianserin acts in human by stopping the action of serotonin, a chemical that transmits messages between nerve cells. The researchers found that when they gave mianserin to worms that had genetic mutations that stopped serotonin production or its uptake by nerve cells, it had little or no effect. It also had little or no effect on worms that lacked proteins on the surface of their cells that bind to serotonin or another messenger chemical called octopamine, which acts with serotonin to signal the presence or absence of food.

Mianserin also had little effect on worms whose lifespan had already been increased by reducing food intake. However, mianserin itself did not cause the worms to reduce their food intake.

What interpretations did the researchers draw from these results?

The researchers concluded that mianserin can increase the lifespan of adult nematode worms. The researchers suggested that mianserin affects the chemical signalling pathways that allow the worm to detect the presence or absence of food. This may mimic the effects of starvation, even when the worms have access to plenty of food.

What does the NHS Knowledge Service make of this study?

Although the results of this research are of good quality, they do not necessarily mean that mianserin will have the same effect on humans, who are much more complex organisms. The researchers now plan to look at the effects of mianserin on mice. However, as mice have longer lifespans than Caenorhabditis elegans, these experiments will take longer to do, so it will be a while until it is known whether mianserin has an effect on more complex animals.

Although BBC news reports that this could mean there is a similar gene in humans that could be targeted to control lifespan, science is many years from identifying such a gene or knowing how to influence it in this way.

Sir Muir Gray adds...

Good news for worms.