Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria, Australia.
Curr Aging Sci. 2021;14(2):118-123. doi: 10.2174/1874609813999210104203614.
The antidepressant Mianserin has been shown to extend the lifespan of Caenorhabditis elegan (C. elegan), a well-established model organism used in ageing research. The extension of lifespan in C. elegan was shown to be dependent on increased expression of the scaffolding protein (ANK3/unc-44). In contrast, antidepressant use in humans is associated with an increased risk of death. The C. elegan elegan in the laboratory are fed Escherichia coli (E. coli), a diet high in protein and low in carbohydrate, whereas a typical human diet is high in carbohydrates. We hypothesized that dietary carbohydrates might mitigate the lifespan-extension effect of mianserin.
To investigate the effect of glucose added to the diet of C. elegan on the lifespan-extension effect of mianserin.
Wild-type Bristol N2 and ANK3/unc-44 inactivating mutants were cultured on agar plates containing nematode growth medium and fed E. coli. Treatment groups included (C) control, (M50) 50 μM mianserin, (G) 73 mM glucose, and (M50G) 50 μM mianserin and 73 mM glucose. Lifespan was determined by monitoring the worms until they died. Statistical analysis was performed using the Kaplan-Meier version of the log-rank test.
Mianserin treatment resulted in a 12% increase in lifespan (P<0.05) of wild-type Bristol N2 worms but reduced lifespan by 6% in ANK3/unc-44 mutants, consistent with previous research. The addition of glucose to the diet reduced the lifespan of both strains of worms and abolished the lifespan-extension by mianserin.
The addition of glucose to the diet of C. elegan abolishes the lifespan-extension effects of mianserin.
抗抑郁药米氮平已被证明能延长秀丽隐杆线虫（C. elegans）的寿命，秀丽隐杆线虫是一种用于衰老研究的成熟模式生物。秀丽隐杆线虫的寿命延长依赖于支架蛋白（ANK3/unc-44）表达增加。相比之下，抗抑郁药在人类中的使用与死亡风险增加有关。实验室中的秀丽隐杆线虫食用的是大肠杆菌（E. coli），这种饮食高蛋白、低碳水化合物，而典型的人类饮食则富含碳水化合物。我们假设饮食中的碳水化合物可能会减轻米氮平的寿命延长效应。
研究添加葡萄糖到秀丽隐杆线虫饮食中对米氮平寿命延长效应的影响。
野生型 Bristol N2 和 ANK3/unc-44 失活突变体在含有线虫生长培养基的琼脂平板上培养，并喂食大肠杆菌。处理组包括（C）对照、（M50）50 μM 米氮平、（G）73 mM 葡萄糖和（M50G）50 μM 米氮平和 73 mM 葡萄糖。通过监测线虫直到它们死亡来确定寿命。统计分析采用 Kaplan-Meier 版本的对数秩检验。
米氮平处理使野生型 Bristol N2 线虫的寿命延长了 12%（P<0.05），但使 ANK3/unc-44 突变体的寿命缩短了 6%，这与之前的研究一致。在饮食中添加葡萄糖降低了两种菌株线虫的寿命，并消除了米氮平的寿命延长作用。
在秀丽隐杆线虫的饮食中添加葡萄糖会消除米氮平的寿命延长作用。
