An engineering approach to extending lifespan in C. elegans.
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.
Departments of Genetics and Developmental Biology, Stanford University Medical Center, Stanford, California, United States of America.
Dror
D
Sagi
Stuart K
SK
Kim
D000375:Aging / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D008136:Longevity / Q000235:genetics / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics; D010269:Paraquat / Q000494:pharmacology; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics
D029961:Zebrafish Proteins; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D010269:Paraquat