If it exists, it must be a tenuous link, right? Well, at least in C. elegans, it is definitely not. Linda Buck and colleagues revealed, in a recent Nature article that drugs modulating the serotonin system in the worm can increase lifespan. Caloric restriction has been a well-documented means to enhance longevity in animals ranging from rodents to worms. We have only recently begun to mechanistically understand why eating less allows us to live longer (remember the sirtuin genes?)

In this latest study, the authors found that a compound typically used as an antidepressant, called mirtazapine and commercially known in the US as Remeron, increased lifespan in the worm by 31% through an inhibition of the 5-HT2 receptor for the neurotransmitter serotonin. This occurred in a dose-dependent manner. Several compounds in the same family (with similar modes of action) failed to increase lifespan in worms harboring mutations in genes causing a disruption of the serotonin system, like in the synthesis enzyme tryptophan hydroxylase or the serotonin reuptake transporter.

In an attempt to link these mechanisms to those typically associated with lifespan extension in the worm, Buck and colleagues demonstrated that treating worms with the antidepressant after caloric restriction failed to increase lifespan beyond that which occurred following caloric restriction alone. In addition, treatment with the drug had little effect on lifespan in worms expressing mutant proteins required to reap the benefits of caloric restriction.

Since serotonin is a neuromodulator that affects a variety of neuronal functions, including food-intake regulation, altering the serotonin system may cause the worm to enter a state of “perceived starvation” that, despite adequate food intake, would still activate the signaling mechanisms responsible for inducing an extended lifespan.

Whether or not this mechanism will hold up in humans is anyone’s guess; the only evidence that it might do so comes from reports of an increased appetite in those taking the same class of antidepressants as was used in the Nature study. If it does turn out to be an evolutionarily conserved pathway in humans, it seems like this mechanism could be a coup for Big Pharma. With antidepressants being prescribed at alarmingly high rates (as of 2002, 11% of women and 5% of men in the non-institutionalized population take anti-depressants), and with those customers living longer because of their prescription filling, Big Pharma could have what Big Tobacco never had: an addictive (at the least psychologically) product that makes more money for the company because it causes its customers to live longer.

Petrascheck, M., Ye, X., & Buck, L. (2007). An antidepressant that extends lifespan in adult Caenorhabditis elegans Nature, 450 (7169), 553-556 DOI: 10.1038/nature05991