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Genetic analysis of hyl-1, the C. elegans homolog of LAG1/LASS1

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Abstract

Yeast LAG1 was one of the first longevity genes found. Subsequent analysis showed that it encodes a component of ceramide synthase. Homologs of LAG1 have been identified in all eukaryotes examined for their presence, and multiple homologs are the norm. In human and mouse, the LAG1 counterpart is called LASS1. The involvement of this gene in determining yeast replicative life span led us to ask whether longevity effects could be found in C. elegans. Extended longevity was seen when we used RNAi to decrease expression of the worm homolog of LAG1, termed hyl-1, for Homolog of Yeast Longevity gene. In contrast, neither deletion of the gene nor overexpression resulted in life extension. There was no evidence that hyl-1 interacts with the insulin/IGF-1 like signaling pathway to specify longevity or dauer formation, nor were effects on stress resistance detected. Gene expression of hyl-1 homologs was altered in the deletion mutant and by RNAi, showing distinct evidence for compensation at the transcript level. These regulatory changes may explain the subtle phenotypic effects found under the conditions studied here.

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Abbreviations

IIL:

insulin/IGF-1 like

IGF:

insulin-like growth factor 1

RNAi:

RNA interference

PCR:

poymerase chain reaction

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Acknowledgments

This work was supported by grants from the National Institutes of Health (NIH), AG16219 to T.E.J. and AG006168 to S.M.J. Some nematode strains were provided by the Caenorhabditis Genetics Center which is funded by the National Center for Research Resources (NCRR) of the NIH. We would like to thank Heather Greer, Sarah Hegi, Ibett Hynek, and Chris Link for technical help and Lina Obeid for permission to cite her unpublished work. Address correspondence to Thomas E. Johnson, PhD, Institute for Behavioral Genetics, Campus Box 447, University of Colorado, Boulder, CO 80309.

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Author notes

  1. James Jiang & S. Michal Jazwinski

    Present address: Department of Medicine, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

Authors and Affiliations

  1. Institute for Behavioral Genetics, University of Colorado at Boulder, Boulder, CO, 80309, USA

    Patricia Tedesco & Thomas E. Johnson

  2. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center in New Orleans, New Orleans, LA, USA

    James Jiang, Jinqing Wang & S. Michal Jazwinski

  3. Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, 80309, USA

    Thomas E. Johnson

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  1. Patricia Tedesco
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  2. James Jiang
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  4. S. Michal Jazwinski
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  5. Thomas E. Johnson
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Correspondence to Patricia Tedesco.

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Tedesco, P., Jiang, J., Wang, J. et al. Genetic analysis of hyl-1, the C. elegans homolog of LAG1/LASS1 . AGE 30, 43–52 (2008). https://doi.org/10.1007/s11357-008-9046-3

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  • DOI: https://doi.org/10.1007/s11357-008-9046-3

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