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.

Highlights

  • The nematorde Caenorhabditis elegans has become a well-established model organism to identify compounds that may be capable of extending lifespan in invertebrates, and mammals

  • In conflict with this evidence, recently published findings unexpectedly suggest that mianserin, and additional antidepressants of the serotonin antagonist type might extend C.elegans lifespan [24], which would surprisingly implicate that obesity promotes longevity

  • To replicate the findings of previously published experiments by Petrascheck and colleagues [24], we have we have applied both compounds described to be life-extending in the original paper, mianserin and methiothepin, to Bristol N2 C.elegans which in our case were maintained on solid-phase agar media, as described in Material and Methods

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Summary

Introduction

The nematorde Caenorhabditis elegans has become a well-established model organism to identify compounds that may be capable of extending lifespan in invertebrates, and mammals. Obesity has been shown to decrease life span in humans [35] as well as C. elegans [25], while in both species serotonin signalling has been implicated in body fat accumulation [36].

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