Antidepressant found to extend lifespan in roundworms by 30%

November 22nd, 2007 - 1:19 pm ICT by admin  

London, Nov 22 (ANI): Researchers at Howard Hughes Medical Institute (HHMI) have discovered that an antidepressant can extend the lifespan of adult roundworms by up to 30 percent.

HHMI researcher Linda B. Buck and her colleagues reported that the antidepressant drug Mianserin may be doing this by mimicking the effects of caloric restriction, which has been shown to retard the effects of aging in a variety of animals ranging from worms and flies to mammals.

Our studies indicate that lifespan extension by mianserin involves mechanisms associated with lifespan extension by dietary restriction. We don’t have an explanation for this. All we can say is that if we give the drug to caloric restricted animals, it doesn’t increase their lifespan any further. That suggests the same mechanism may be involved, Nature quoted Buck, as saying.

Authors are not clear exactly how mianserin staves off the effects of aging. However, the drug appears to act the same way in both C. elegans and humans: by blocking certain receptors for the neurotransmitter serotonin, a chemical that cells use to communicate, helping them regulate many functions, including mood, appetite, and sensory perception.

According to Buck, it was a surprise to find that a drug used to treat depression in humans could extend lifespan in worms. The researchers discovered that in addition to inhibiting certain serotonin receptors in the worm, it also blocked receptors for another neurotransmitter, octopamine.

She said that a number of observations support the idea that serotonin and octopamine may complement one another in a physiological context with serotonin signaling the presence of food and octopamine signaling its absence or a state of starvation.

Roundwrorms, 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. 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, she said.

The research team focused on the effects of mianserin based on the results of a search through 88,000 chemicals for agents that extended the lifespan of nematodes. They found 115 such chemicals. In follow-up studies of one chemical, they found four additional compounds, including mianserin that extended lifespan by 20-33 percent. All four compounds inhibit certain types of serotonin receptors in humans.

We screened a wide variety of chemicals without knowing anything about them except that they were small molecules. By screening adult animals with this extremely varied panel of compounds, we hoped to identify drugs that could increase lifespan in adults, even though some might have a deleterious effect on the developing animal, Buck said.

She added that by identifying drugs that influence lifespan, it might be possible to home in on how those drugs act and contribute to a growing body of knowledge about the genetic mechanisms of aging.
Other researchers have done beautiful work using molecular genetic approaches to identify genes involved in aging. We decided to take a chemical approach. By finding chemicals that enhance longevity, and then finding the targets of those chemicals, it may be possible to identify additional genes important in aging. In addition, the chemical approach could point to drugs suitable for testing in mammals, she said. (ANI)

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