Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan.

Reducing Reactive Oxygen Species (ROS) production can extend animal lifespan by silencing mitochondrial genes through RNAi mediated. Lower ATP levels may activate genes that regulate worm lifespan. Insulin/IGF-1 receptor-like molecule is supposed to double animal lifespan and genes such as daf-2 encoding this molecule when mutated in Caenorhabtidis elegans can also extend its lifespan.

The authors optimized an assay to monitor ROS resistance in worms using the ROS- generating chemical paraquat. Eighty four genes were identified from chromosomes III and IV by developing a functional genomic RNAi screen. The experiment included C. elegans being cultured in a medium containing bacteria expressing interfering dsRNA for the target gene. The worm was reared until L4 stage and a comparison was made between a culture chemically treated with paraquat and another one non- treated. The species strain was rrf- 3 (pk1426), Polymerase Chain Reaction fragment was cloned in the L4440 vector and primers corresponding to a genomic region in daf- 2 and daf- 18 were obtained.

The study found that mutations in daf2 and daf18 can alter sensitivity toward paraquat toxicity. Moreover a screening method for identification of genes involved in regulation of animal lifespan has been created.

Reference: Yongsoon K,Hong S Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. (2007) Aging Cell 6, pp 489-503 DOI: 10.1111/J. 1474-9726.2007.00302.x.

Patricia Lemos