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PLoS Genet. 2012;8(6):e1002780. doi: 10.1371/journal.pgen.1002780. Epub 2012 Jun 21.

An engineering approach to extending lifespan in C. elegans.

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1
Departments of Genetics and Developmental Biology, Stanford University Medical Center, Stanford, California, United States of America.

Abstract

We have taken an engineering approach to extending the lifespan of Caenorhabditis elegans. Aging stands out as a complex trait, because events that occur in old animals are not under strong natural selection. As a result, lifespan can be lengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally, we extended lifespan by increasing the activity of four endogenous worm aging pathways. Next, we used a modular approach to extend lifespan by combining components. Finally, we used cell- and worm-based assays to analyze changes in cell physiology and as a rapid means to evaluate whether multi-component transgenic lines were likely to have extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new framework for lifespan extension that goes beyond the constraints of the worm genome.

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PMID:
22737090
PMCID:
PMC3380832
DOI:
10.1371/journal.pgen.1002780
[Indexed for MEDLINE]
Free PMC Article

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