Caenorhabditis elegans is widely used as a model for investigation of the relationships between aging, nutrient restriction and signalling via the DAF-2 (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity of the glucose transporters that may link these processes is unknown. We unexpectedly find that of the eight putative GLUT (glucose transporter)-like genes only the two splice variants of one gene have a glucose transport function in an oocyte expression system. We have named this gene fgt-1 (facilitated glucose transporter, isoform 1). We show that knockdown of fgt-1 RNA leads to loss of glucose transport and reduced glucose metabolism in wild-type worms. The FGT-1 glucose transporters of C. elegans thus play a key role in glucose energy supply to C. elegans. Importantly, knockdown of fgt-1 leads to an extension of lifespan equivalent, but not additive, to that observed in daf-2 and age-1 mutant worms. The results of the present study are consistent with DAF-2 and AGE-1 signalling stimulating glucose transport in C. elegans and this process being associated with the longevity phenotype in daf-2 and age-1 mutant worms. We propose that fgt-1 constitutes a common axis for the lifespan extending effects of nutrient restriction and reduced insulin-like peptide signalling.
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Univ Massachusetts, Sch Med, Program Gene Funct & Express, Program Mol Med, Worcester, MA 01605 USAUniv Massachusetts, Sch Med, Program Gene Funct & Express, Program Mol Med, Worcester, MA 01605 USA
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NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USANYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Gusarov, Ivan
Shamovsky, Ilya
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NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USANYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Shamovsky, Ilya
Pani, Bibhusita
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NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USANYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Pani, Bibhusita
Gautier, Laurent
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NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USANYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Gautier, Laurent
Eremina, Svetlana
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Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, RussiaNYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Eremina, Svetlana
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Katkova-Zhukotskaya, Olga
Mironov, Alexander
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Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, RussiaNYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Mironov, Alexander
Makarov, Alexander A.
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Russian Acad Sci, Engelhardt Inst Mol Biol, Moscow, RussiaNYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
Makarov, Alexander A.
Nudler, Evgeny
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NYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA
NYU, Howard Hughes Med Inst, Sch Med, New York, NY 10016 USANYU, Dept Biochem & Mol Pharmacol, Sch Med, New York, NY 10016 USA