Lipidomics data.

Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr96[1] null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr96[1] mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor[1] mutation results in females that lack the germ-line and produce no eggs. Maternal tudor[1] mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w[1118] mutant mated females, but did not increase life span in w[1118] mutant virgin females. Mifepristone decreased egg production in w[1118] mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white[+] and mini-white[+] strains. Backcrossing of mini-white[+] transgenes into the w[1118] background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms.

交配行为与雌性接收雄性性肽（Sex Peptide）激素，会导致雌性果蝇（Drosophila）的产卵量提升、中肠体积增大以及寿命缩短。给已交配的雌性果蝇喂食合成类固醇类药物米非司酮（mifepristone），可降低其产卵量、缩小中肠体积并延长寿命。本研究通过检测多种基因突变，探究米非司酮发挥作用的潜在分子机制。果蝇Dhr96是一种激素受体，同时是中肠脂质摄取与代谢的关键正向调控因子。Dhr96[1]纯合缺失突变可延长雌性果蝇的寿命，并削弱米非司酮对寿命的影响，这提示Dhr96[1]突变与米非司酮可能部分通过相同的分子机制发挥作用。脂质组学（lipidomics）分析显示，交配会提升果蝇全身甘油三酯（triglycerides）及甘油三酯结合型脂肪酸的水平，而米非司酮可逆转上述变化。母体tudor[1]突变会导致雌性果蝇缺失生殖系且无法产卵。母体tudor[1]突变可延长已交配雌性果蝇的寿命，虽能削弱但并未消除交配与米非司酮对寿命的影响。这表明产卵量降低或许与米非司酮的延寿效应相关，但并非其发挥延寿作用的必要条件。米非司酮可延长w[1118]突变型已交配雌性果蝇的寿命，但无法延长w[1118]突变型处女雌性果蝇的寿命。米非司酮会降低w[1118]突变型处女雌性果蝇的产卵量，这说明产卵量降低并非米非司酮实现延寿的充分条件。米非司酮可延长部分（而非全部）white[+]与mini-white[+]品系处女雌性果蝇的寿命。将mini-white[+]转基因回交至w[1118]遗传背景中，不足以使处女雌性果蝇对米非司酮产生延寿响应。综合上述实验结果，本研究数据支持以下假说：米非司酮的延寿机制涉及脂质摄取与/或代谢的减弱；同时提示米非司酮在已交配与处女雌性果蝇中实现延寿的分子机制存在部分差异。