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LETTER TO THE EDITOR |
Ghent University Belgium
Address correspondence to Jacques R. Vanfleteren, Department of Biology, Ghent University, K. L. Ledeganckstraat 35, B-9000 Ghent, Belgium. E-mail: jacques.vanfleteren{at}ugent.be
To the Editor:
Many genes regulate the aging rate of the nematode Caenorhabditis elegans (1–3). Reduced Ins/IGF-1 (insulin-like growth factor-1) signaling, which is the most intensively studied mechanism of life extension in C. elegans, also increases the life span of flies and mice (4,5). A recent report showed that daf-2 RNAi treatment and germ-line ablation of worms carrying the daf-2(e1368) hypomorphic mutation in the gene encoding the C. elegans Ins/IGF-1 receptor further increases their life span up to 6.0-fold (6). These authors claimed that this was a record life extension, missing an earlier result (7).
As in a wide range of animals, the life span of C. elegans can also be increased by caloric restriction. Worms grown in a semidefined axenic medium (in the absence of bacteria, the normal food source of C. elegans) have a more than doubled mean life span and display similar changes in physiology, stress defense, and metabolism as worms restricted by eat-mutation or by growth in liquid cultures supplied with less Escherichia coli (8,9). We asked whether this type of life extension is distinct from extension via the DAF-2 pathway and might be combined with reduced Ins/IGF-1 signaling to surpass both the Arantes-Oliveira record and our own former record. We reported a 6.3-fold extension of mean life for a daf-2 mutant grown with an axenic food source (7), and the relative life extension may have been even greater had we excluded development; thus, we collected additional data to address this issue. We found an extension of mean adult life span of 85% in daf-2 mutants when grown on a bacterial diet. Growth in axenic medium results in an extension of mean adult life by 170% for the wild type and 310% for daf-2(e1370). Thus, the mean adult life span of these extremely long-lived mutants is even more sensitive to axenic-based life extension and exceeds that of bacterially grown wild-type worms by a factor of 7.5 (Figure 1). This is the maximal mean life extension ever observed in any animal, and is thus the record mean life-span extension. Apparently, daf-2 mutation and axenic-based caloric restriction act synergistically to increase C. elegans longevity. We wondered if these ultralong lives would be specific to daf-2, or if these could also be found in worms carrying other life-extension mutations. We tested the mean life spans of the single mutants age-1, gro-1, and clk-1, and of the double mutants age-1; gro-1 and clk-1; daf-2 and found that axenic growth also increased the life span of these mutants substantially relative to the controls (Figure 2). The mean life expectancy of these mutant strains was increased by factors ranging from 1.5 to 2.7, similar to observations in monoxenic cultures. We therefore conclude that the ultralong life span of long-lived mutants grown in axenic medium is not specific for daf-2.
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Acknowledgments
K.H. and B.P.B. are postdoctoral fellows with the Fund for Scientific Research-Flanders, Belgium. This research was supported by grants from Ghent University and the Fund for Scientific Research–Flanders.
References
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