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Biochemical, Molecular, and Genetic Mechanisms

Feeding Drosophila a Biotin-Deficient Diet for Multiple Generations Increases Stress Resistance and Lifespan and Alters Gene Expression and Histone Biotinylation Patterns^1–3,

⁴ Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583-0806; ⁵ Edward A. Doisy Department of Biochemistry and Molecular Biology and ⁶ Department of Pharmacological and Physiological Sciences, Saint Louis University School of Medicine, St. Louis, MO 63104; ⁷ School of Biological Sciences, University of Nebraska, Lincoln, NE 68588-0118; and ⁸ Department of Food Science and Technology, University of Nebraska, Lincoln, NE 68583-0919

^* To whom correspondence should be addressed. E-mail: jzempleni2{at}unl.edu.

Energy restriction increases stress resistance and lifespan in Drosophila melanogaster and other species. The roles of individual nutrients in stress resistance and longevity are largely unknown. The vitamin biotin is a potential candidate for mediating these effects, given its known roles in stress signaling and gene regulation by epigenetic mechanisms, i.e. biotinylation of histones. Here, we tested the hypothesis that prolonged culture of Drosophila on biotin-deficient (BD) medium increases stress resistance and lifespan. Flies were fed a BD diet for multiple generations; controls were fed a biotin-normal diet. In some experiments, a third group of flies was fed a BD diet for 12 generations and then switched to control diets for 2 generations to eliminate potential effects of short-term biotin deficiency. Flies fed a BD diet exhibited a 30% increase in lifespan. This increase was associated with enhanced resistance to the DNA-damaging agent hydroxyurea and heat stress. Also, fertility increased significantly compared with biotin-normal controls. Biotinylation of histones was barely detectable in biotin-deprived flies, suggesting that epigenetic events might have contributed to effects of biotin deprivation.