An Engineering Approach to Extending Lifespan in C. elegans
- Authors
- Sagi, D., and Kim, S.K.
- ID
- ZDB-PUB-120705-19
- Date
- 2012
- Source
- PLoS Genetics 8(6): e1002780 (Journal)
- Registered Authors
- Keywords
- Zebrafish, Caenorhabditis elegans, Aging, Oxidative damage, Engineering and technology, Gene expression, Genetic engineering, Mitochondria
- MeSH Terms
-
- Aging/genetics
- Aldehyde Dehydrogenase/genetics
- Animals
- Animals, Genetically Modified*
- Caenorhabditis elegans/cytology
- Caenorhabditis elegans/genetics*
- Caenorhabditis elegans/physiology*
- Cell Survival/drug effects
- Gene Expression
- Humans
- Longevity*/genetics
- Longevity*/physiology
- Oxidative Stress/genetics
- Paraquat/pharmacology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- PubMed
- 22737090 Full text @ PLoS Genet.
- CTD
- 22737090
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.