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Published November 3, 2009 | Published + Supplemental Material
Journal Article Open

Water- and nutrient-dependent effects of dietary restriction on Drosophila lifespan

Abstract

Dietary restriction (DR) is a widely conserved intervention leading to lifespan extension. Despite considerable effort, the mechanisms underlying DR remain poorly understood. In particular, it remains unclear whether DR prolongs life through conserved mechanisms in different species. Here, we show that, in the most common experimental conditions, lifespan extension by DR is abolished by providing Drosophila with ad libitum water, without altering food intake, indicating that DR, as conventionally studied in flies, is fundamentally different from the phenomenon studied in mammals. We characterize an alternative dietary paradigm that elicits robust lifespan extension irrespective of water availability, and thus likely represents a more relevant model for mammalian DR. Our results support the view that protein:carbohydrate ratio is the main dietary determinant of fly lifespan. These findings have broad implications for the study of lifespan and nutrition.

Additional Information

© 2009 by the National Academy of Sciences. Edited by David L. Denlinger, The Ohio State University, Columbus, OH, and approved September 4, 2009 (received for review July 17, 2009). Published online before print October 19, 2009. Author contributions: W.W.J., G.B.C., B.M.Z., T.B., and S.B. designed research; W.W.J., G.B.C., B.M.Z., and E.M.M. performed research; W.W.J., G.B.C., and B.M.Z. analyzed data; and W.W.J. and G.B.C. wrote the paper. We wish to dedicate this work to the life and career of our beloved friend and mentor, Seymour Benzer. We thank A.W. Chang for technical assistance; M. Piper and L. Partridge (University College London) for the Dahomey fly line; and S.M. Lee, S.J. Simpson (University of Sydney), P. Kapahi (Buck Institute for Age Research), and H.-D. Wang (National Tsing Hua University) for comments on the manuscript. This work was supported by a postdoctoral fellowship from the John Douglas French Alzheimer's Foundation (to W.W.J.); a Lawrence L. and Audrey W. Ferguson Fellowship (to G.B.C.); and Grants from the National Institutes of Health (1R15AG027749–01A1 to T.B., 1K99AG030493 to W.W.J., and AG16630, AG24366, and DK070154 to S.B.), National Science Foundation (MCB-0418479 to S.B.), and the Ellison Foundation (to S.B.). This article contains supporting information online at www.pnas.org/cgi/content/full/0908016106/DCSupplemental.

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Published - Ja2009p6257P_Natl_Acad_Sci_Usa.pdf

Supplemental Material - Ja2009p6257P_Natl_Acad_Sci_Usa_supp.pdf

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