antidepressants of the serotonin-antagonist type increase body fat and decrease lifespan of adult caenorhabditis elegansserotonin-antagonist类型的抗抑郁药物增加脂肪和减少成人线虫的寿命.pdf

Antidepressants of the Serotonin-Antagonist Type Increase Body Fat and Decrease Lifespan of Adult Caenorhabditis elegans 1 1,2 Kim Zarse , Michael Ristow * ¨ 1 Institute of Nutrition, University of Jena, Jena, Germany, 2 German Institute of Human Nutrition, Potsdam-Rehbrucke, Germany 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 . 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. Citation: Zarse K, Ristow M (2008) Antidepressants of the Serotonin-Antagonist Type Increase Body Fat and Decrease Lifespan of Adult Caenorhabditis elegans. PLoS ONE 3(12): e4062. doi:10.1371/journal.pone.0004062 ´ Editor: Georges Chapo