Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-7-19
pubmed:abstractText
Genetic studies in many organisms suggest that an increased animal lifespan phenotype is often accompanied by enhanced resistance toward reactive oxygen species (ROS). In Caenorhabditis elegans, mutations in daf-2, which encode an insulin/insulin-like growth factor 1 receptor-like molecule, lead to an extended animal lifespan and increased resistance to ROS. We have optimized an assay to monitor ROS resistance in worms using the ROS-generating chemical paraquat. We have employed this assay to screen the RNAi library along chromosomes III and IV for genes that, when silenced, confer paraquat resistance. The positive RNAi clones were subsequently screened for a lifespan extension phenotype. Using this approach, we have identified 84 genes that, when inactivated by RNAi, lead to significant increases in animal lifespan. Among the 84 genes, 29 were found to act in a manner dependent on daf-16. DAF-16, a forkhead transcription factor, is known to integrate signals from multiple pathways, including the daf-2 pathway, to regulate animal lifespan. Most of the 84 genes have not been previously linked to aging, and potentially participate in important cellular processes such as signal transduction, cell-cell interaction, gene expression, protein degradation, and energy metabolism. Our screen has also identified a group of genes that potentially function in a nutrient-sensing pathway to regulate lifespan in C. elegans. Our study provides a novel approach to identify genes involved in the regulation of aging.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1474-9718
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-503
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan.
pubmed:affiliation
Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural