Antidepressant lengthens worm lifespan
"An antidepressant drug lengthens tiny worms' lives and offers hope of humans living longer too, US scientists say.
In the study, detailed in journal Nature, nematode worms were exposed to 88,000 chemicals in turn and mianserin extended lifespan by almost a third.
The drug seems to mimic the effects on the body of the only known animal long-life regime - virtual starvation. [BBC]"
Mianserin is a tricyclic antidepressant. Molecule shown above.
The researchers don't know why worms exposed to mianserin lived about 30% longer than their untreated counterparts. The researchers took an empirical approach, exposing worms to thousands of different small molecules and noting the effects on survical. Head researcher Linda Buck of the Howard Hughs Medical Institute shared some preliminary hypotheses with Science Daily:
Buck said it was a surprise to find that a drug used to treat depression in humans could extend lifespan in worms. The researchers in Buck's lab found that in addition to inhibiting certain serotonin receptors in the worm, it also blocked receptors for another neurotransmitter, octopamine.
A number of observations support the idea that serotonin and octopamine may complement one another in a physiological context, Buck explained, with serotonin signaling the presence of food and octopamine signaling its absence or a state of starvation. C. elegans, for instance, usually only lays eggs when food is on hand. But serotonin stimulates egg laying in the absence of food, while octopamine inhibits egg laying even when food is nearby. Another example of interplay between the two chemicals is that pharyngeal pumping, the mechanism by which worms ingest food, is jump-started by serotonin and thwarted by octopamine.
"In our studies, mianserin had a much greater inhibitory effect on the serotonin receptor than the octopamine receptor," she said. "One possibility is that there is a dynamic equilibrium between serotonin and octopamine signaling and the drug tips the balance in the direction of octopamine signaling, producing a perceived, though not real, state of starvation that activates aging mechanisms downstream of dietary restriction." [SD]