Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Author Coleen Murphy, Steven McCarroll, Cornelia Bargmann, Andrew Fraser, Ravi Kamath, Julie Ahringer, Hao Li, Cynthia Kenyon Publication Year 2003 Type Journal Article Abstract Ageing is a fundamental, unsolved mystery in biology. DAF-16, a FOXO-family transcription factor, influences the rate of ageing of Caenorhabditis elegans in response to insulin/insulin-like growth factor 1 (IGF-I) signalling. Using DNA microarray analysis, we have found that DAF-16 affects expression of a set of genes during early adulthood, the time at which this pathway is known to control ageing. Here we find that many of these genes influence the ageing process. The insulin/IGF-I pathway functions cell non-autonomously to regulate lifespan, and our findings suggest that it signals other cells, at least in part, by feedback regulation of an insulin/IGF-I homologue. Furthermore, our findings suggest that the insulin/IGF-I pathway ultimately exerts its effect on lifespan by upregulating a wide variety of genes, including cellular stress-response, antimicrobial and metabolic genes, and by downregulating specific life-shortening genes. Keywords Animals, Gene Expression Regulation, Developmental, Signal Transduction, Transcription, Genetic, Cluster Analysis, Transcription Factors, Oligonucleotide Array Sequence Analysis, RNA Interference, Time Factors, Stress, Physiological, Aging, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Feedback, Physiological, Insulin, Longevity, Genes, Helminth, Receptor, Insulin, Insulin-Like Growth Factor I, Response Elements, RNA, Helminth Journal Nature Volume 424 Issue 6946 Pages 277-83 Date Published 07/2003 Alternate Journal Nature Google ScholarBibTeXEndNote X3 XML