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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics*
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Aging / physiology
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Animals
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Caenorhabditis elegans / genetics*
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Caenorhabditis elegans / immunology
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Caenorhabditis elegans / physiology
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Caenorhabditis elegans Proteins / genetics*
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Caenorhabditis elegans Proteins / metabolism*
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Cluster Analysis
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Feedback, Physiological
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Forkhead Transcription Factors
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Gene Expression Regulation, Developmental
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Genes, Helminth / genetics*
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Genes, Helminth / physiology
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Insulin / metabolism
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Insulin-Like Growth Factor I / metabolism
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Longevity / genetics*
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Longevity / physiology
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Oligonucleotide Array Sequence Analysis
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RNA Interference
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RNA, Helminth / analysis
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RNA, Helminth / genetics
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Receptor, Insulin / agonists
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Receptor, Insulin / genetics
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Receptor, Insulin / metabolism
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Response Elements / genetics
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Signal Transduction
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Stress, Physiological / genetics
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Stress, Physiological / physiopathology
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Time Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / genetics
Substances
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Insulin
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RNA, Helminth
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Transcription Factors
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daf-16 protein, C elegans
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Insulin-Like Growth Factor I
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DAF-2 protein, C elegans
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Receptor, Insulin