Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
doi: 10.1038/nature01789
pmid: 12845331
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
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.
- University of Cambridge United Kingdom
- University of California, San Francisco United States
Feedback, Physiological, Aging, Time Factors, Longevity, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Response Elements, Receptor, Insulin, Stress, Physiological, Animals, Cluster Analysis, Insulin, RNA Interference, Insulin-Like Growth Factor I, RNA, Helminth, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Genes, Helminth, Oligonucleotide Array Sequence Analysis, Signal Transduction
Feedback, Physiological, Aging, Time Factors, Longevity, Gene Expression Regulation, Developmental, Forkhead Transcription Factors, Response Elements, Receptor, Insulin, Stress, Physiological, Animals, Cluster Analysis, Insulin, RNA Interference, Insulin-Like Growth Factor I, RNA, Helminth, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Genes, Helminth, Oligonucleotide Array Sequence Analysis, Signal Transduction
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