Yamada Ryuichi, Deshpande Sonali A, Keebaugh Erin S, Ehrlich Margaux R, Soto Obando Alina, Ja William W
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.
Present address: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
J Gerontol A Biol Sci Med Sci. 2017 Feb;72(2):173-180. doi: 10.1093/gerona/glw072. Epub 2016 Apr 19.
The Drosophila GeneSwitch system facilitates the spatial and temporal control of gene expression through dietary supplementation of mifepristone (RU486). Because experimental and control groups differ only by treatment with RU486, confounding results from using flies of different genetic backgrounds are eliminated, making GeneSwitch especially useful in studies of aging. However, the effect of RU486 itself on longevity has not been well characterized, particularly in relation to nutritional states known to affect lifespan. Here, we show that RU486 has dose- and diet-dependent effects on longevity in both sexes. On low nutrient diets, RU486 supplementation reduces total food consumption, perhaps exacerbating undernutrition to shorten life. RU486 also inhibits proboscis extension responses to low nutrient diets, suggesting that RU486 has an aversive taste which leads to decreased food consumption and diminished longevity. RU486 is not detrimental to fly lifespan on high nutrient food, correlating with reduced effects of the drug on palatability and total consumption on rich diets. Our results highlight the critical importance of considering how food palatability and nutrient intake might be altered by dietary or drug manipulations in studies of aging and behavior.
果蝇基因开关系统通过饮食补充米非司酮（RU486）促进基因表达的时空控制。由于实验组和对照组仅在是否用RU486处理上存在差异，因此消除了使用不同遗传背景果蝇所产生的混杂结果，这使得基因开关在衰老研究中特别有用。然而，RU486本身对寿命的影响尚未得到充分表征，特别是与已知会影响寿命的营养状态相关的影响。在这里，我们表明RU486对两性的寿命具有剂量和饮食依赖性影响。在低营养饮食中，补充RU486会减少总食物消耗，这可能会加剧营养不良从而缩短寿命。RU486还会抑制对低营养饮食的伸吻反应，这表明RU486具有厌恶味道，会导致食物消耗减少和寿命缩短。在高营养食物上，RU486对果蝇寿命无害，这与该药物对丰富饮食的适口性和总消耗量的影响降低相关。我们的结果突出了在衰老和行为研究中考虑饮食或药物操作如何改变食物适口性和营养摄入的至关重要性。
