Antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult Caenorhabditis elegans

Abstract

It was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553-6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan.

Figure 1. Antidepressants of the human serotonin antagonist type do not extend Caenorhabditis elegans lifespan.

Panel A: The antidepressant mianserin shortens C.elegans lifespan at concentrations of 50 µM (dark blue boxes; this concentration was shown extend lifespan in the original publication [ref. 24]), 5 µM (medium blue boxes), and 500 nM (light blue boxes). Untreated control nematodes are depicted by black circles. Panel B: The chemically and functionally related compound methiothepin similarly shortens C.elegans lifespan at concentrations of 10 µM (red boxes; this concentration was shown extend lifespan in the original publication [ref. 24]), 1 µM (orange boxes), and has no significant effect on lifespan at a lower concentration of 100 nM (yellow boxes). Untreated control nematodes are depicted by black circles.

Figure 2. Antidepressants of the human serotonin antagonist type increase Caenorhabditis elegans body fat content.

Panel A: The antidepressant mianserin increases C.elegans body fat content at a concentration of 50 µM (dark blue bar, right side; this concentration was shown extend lifespan in the original publication [ref. 24]) after ten days of treatment; untreated control nematodes are depicted as black bar. Panel B: The related compound methiothepin increases C.elegans body fat content at a concentration of 10 µM (red bar, right side; this concentration was shown extend lifespan in the original publication [ref. 24]) after ten days of treatment; untreated control nematodes are depicted as black bar.