Mifepristone Reduces Food Palatability and Affects Drosophila Feeding and Lifespan.
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.
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.
Ryuichi
R
Yamada
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.|Present address: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, David Geffen School of Medicine, University of California, Los Angeles.
Sonali A
SA
Deshpande
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.
Erin S
ES
Keebaugh
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.
Margaux R
MR
Ehrlich
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida.
Alina
A
Soto Obando
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida. wja@scripps.edu.
William W
WW
Ja
D000818:Animals; D004330:Drosophila / Q000187:drug effects* / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects*; D005260:Female; D005518:Food Preferences / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*
D015735:Mifepristone
Aging; Dietary restriction; Longevity; Nutrition; Palatability