At least in worms

Nov 23, 2007 07:47 GMT  ·  By

It is clear that being sad and stressed all the time drains your energy. And the reverse is also valid. Even more, a team at Howard Hughes Medical Institute (HHMI) found in a research published in journal Nature that an antidepressant, mianserin, can prolong life of adult roundworms, Caenorhabditis elegans, by about 30 %. In fact, the drug imitated the symptoms of caloric restriction, proven to delay aging in 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." said lead researcher Linda B. Buck, a member of the Basic Sciences Division of the Fred Hutchinson Cancer Research Center in Seattle.

The drug could work similarly in both C. elegans and humans: by blocking receptors for the neurotransmitter serotonin, "the feel good hormone" involved in mood, appetite and sensory perception control.

Mianserin 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, 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," explained Buck.

The pharyngeal pumping, through which worms ingest food, is activated by serotonin and stopped 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 team found about 115 chemicals involved in prolonging nematodes' life. 4 chemicals, including mianserin, prolonged life by 20-33 %, and all 4 block certain human serotonin receptors.

"By identifying drugs that influence lifespan, it may be possible to home in on how those drugs act and contribute to a growing body of knowledge about the genetic mechanisms of aging. 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." said Buck.