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Horm Metab Res 2011; 43(10): 687-692
DOI: 10.1055/s-0031-1286308
Original Basic
Georg Thieme Verlag KG Stuttgart · New York

Lonidamine Extends Lifespan of Adult Caenorhabditis elegans by Increasing the Formation of Mitochondrial Reactive Oxygen Species

S. Schmeisser
1   Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
2   Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI), Jena, Germany
,
K. Zarse
1   Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
,
M. Ristow
1   Department of Human Nutrition, Institute of Nutrition, University of Jena, Jena, Germany
3   Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
› Author Affiliations
Further Information

Publication History

received 02 July 2011

accepted 03 August 2011

Publication Date:
19 September 2011 (online)

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Abstract

Compounds that delay aging in model organisms may be of significant interest to antiaging medicine, since these substances potentially provide pharmaceutical approaches to promote healthy lifespan in humans. The aim of the study was to test whether pharmaceutical concentrations of the glycolytic inhibitor lonidamine are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. elegans roundworms were maintained on agar plates and fed E. coli strain OP50 bacteria. Lonidamine was applied to test whether it may promote longevity by quantifying survival in the presence and absence of the compound. In addition, several biochemical and metabolic assays were performed with nematodes exposed to lonidamine. Lonidamine significantly extends both median and maximum lifespan of C. elegans when applied at a concentration of 5 micromolar by 8% each. Moreover, the compound increases paraquat stress resistance, and promotes mitochondrial respiration, culminating in increased formation of reactive oxygen species (ROS). Extension of lifespan requires activation of pmk-1, an orthologue of p38 MAP kinase, and is abolished by co-application of an antioxidant, indicating that increased ROS formation is required for the extension of lifespan by lonidamine. Consistent with the concept of mitohormesis, lonidamine is capable of promoting longevity in a pmk-1 sensitive manner by increasing formation of ROS.

Key words

glucose - nutrition - antioxidants
 

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