Abstract
The C. elegans insulin/IGF-1 (insulin-like growth factor 1) signaling mutant daf-2 recapitulates the dauer metabolic signature—a shift towards lipid and carbohydrate accumulation—which may be linked to its longevity and stress resistance phenotypes. Trehalose, a disaccharide of glucose, is highly upregulated in daf‑2 mutants and it has been linked to proteome stabilization and protection against heat, cold, desiccation, and hypoxia. Earlier studies suggested that elevated trehalose levels can explain up to 43% of the lifespan extension observed in daf-2 mutants. Here we demonstrate that trehalose accumulation is responsible for increased osmotolerance, and to some degree thermotolerance, rather than longevity in daf-2 mutants. This indicates that particular stress resistance phenotypes can be uncoupled from longevity.
Highlights
Lieselot Vandemeulebroucke, Laboratory of Aging Physiology and Molecular Evolution, Department of Biology, Ghent University, Citation: Rasulova, M.; Zečić, A.; Monje Moreno, J.M.; Vandemeulebroucke, L.; Dhondt, I.; Abstract: The C. elegans insulin/IGF-1 signaling mutant daf-2 recapitulates the dauer metabolic signature—a shift towards lipid and carbohydrate accumulation—which may be linked to its longevity and stress resistance phenotypes
Trehalose is synthesized by the transfer of a UDP-glucose to glucose-6-phosphate by trehalose phosphate synthase
As daf-2 longevity has been reported to be dependent on trehalose synthesis [22] which occurs in distinct tissues under control of two tps isoforms, we wondered whether this lifespan phenotype can be attributed to one single tissue or one tps isoform
Summary
Trehalose is synthesized by the transfer of a UDP-glucose to glucose-6-phosphate by trehalose phosphate synthase. Based on transcriptional profiling data [35], both tps genes likely serve specific tissues in the worm: tps-1 seems to be the isoform, which is moderately expressed in most tissues, while tps-2 is highly expressed in the intestine, muscles, and to some extent in the hypodermis and ciliated sensory neurons (Figure 1A). Tps-2p::gfp is strongly expressed in body wall muscles and likely the ciliated sensory neurons, but in contrast to the larval transcriptomics data [35], expression in the intestine and hypodermis is very weak (Figure 1C). A similar tps expression pattern occurs in starved worms, with variable upregulation of tps-1 in the intestine and no clear effect on tps-2 expression [37] Both daf-2 RNAi [38] and starvation [39] result in DAF-16 nuclear localization, explaining the similarity of these patterns. DAF-16 is localized in the cytosol while in daf-2(e1370), it accumulates in the nuclei, irrespective of tps knockdown (Figure S2)
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