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Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan.
Aging Cell 2007; 6(4):489-503AC

Abstract

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.

Authors+Show Affiliations

Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17608836

Citation

Kim, Yongsoon, and Hong Sun. "Functional Genomic Approach to Identify Novel Genes Involved in the Regulation of Oxidative Stress Resistance and Animal Lifespan." Aging Cell, vol. 6, no. 4, 2007, pp. 489-503.
Kim Y, Sun H. Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. Aging Cell. 2007;6(4):489-503.
Kim, Y., & Sun, H. (2007). Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. Aging Cell, 6(4), pp. 489-503.
Kim Y, Sun H. Functional Genomic Approach to Identify Novel Genes Involved in the Regulation of Oxidative Stress Resistance and Animal Lifespan. Aging Cell. 2007;6(4):489-503. PubMed PMID: 17608836.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespan. AU - Kim,Yongsoon, AU - Sun,Hong, Y1 - 2007/07/03/ PY - 2007/7/5/pubmed PY - 2007/10/4/medline PY - 2007/7/5/entrez SP - 489 EP - 503 JF - Aging cell JO - Aging Cell VL - 6 IS - 4 N2 - 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. SN - 1474-9718 UR - https://www.unboundmedicine.com/medline/citation/17608836/Functional_genomic_approach_to_identify_novel_genes_involved_in_the_regulation_of_oxidative_stress_resistance_and_animal_lifespan_ L2 - https://doi.org/10.1111/j.1474-9726.2007.00302.x DB - PRIME DP - Unbound Medicine ER -