Linked Life Data

15308663

Source:http://linkedlifedata.com/resource/pubmed/id/15308663

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2004-10-18
pubmed:abstractText
In the nematode Caenorhabditis elegans, formation of the long-lived dauer larva and adult aging are both controlled by insulin/insulin-like growth factor-1 signaling. Potentially, increased adult life span in daf-2 insulin/insulin-like growth factor-1 receptor mutants results from mis-expression in the adult of a dauer larva longevity program. By using oligonucleotide microarray analysis, we identified a dauer transcriptional signature in daf-2 mutant adults. By means of a nonbiased statistical approach, we identified gene classes whose expression is altered similarly in dauers and daf-2 mutants, which represent potential determinants of life span. These include known determinants of longevity; the small heat shock protein/alpha-crystallins are up-regulated in both milieus. The cytochrome P450, short-chain dehydrogenase/reductase, UDP-glucuronosyltransferase, and glutathione S-transferase (in daf-2 mutants) gene classes were also up-regulated. These four gene classes act together in metabolism and excretion of toxic endobiotic and xenobiotic metabolites. This suggests that diverse toxic lipophilic and electrophilic metabolites, disposed of by phase 1 and phase 2 drug metabolism, may be the major determinants of the molecular damage that causes aging. In addition, we observed down-regulation of genes linked to nutrient uptake, including nhx-2 and pep-2. These work together in the uptake of dipeptides in the intestine, implying dietary restriction in daf-2 mutants. Some gene groups up-regulated in dauers and/or daf-2 were enriched for certain promoter elements as follows: the daf-16-binding element, the heat shock-response element, the heat shock-associated sequence, or the hif-1-response element. By contrast, the daf-16-associated element was enriched in genes down-regulated in dauers and daf-2 mutants. Thus, particular promoter elements appear longevity-associated or aging associated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44533-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15308663-Aging, pubmed-meshheading:15308663-Animals, pubmed-meshheading:15308663-Caenorhabditis elegans, pubmed-meshheading:15308663-Caenorhabditis elegans Proteins, pubmed-meshheading:15308663-Cytochrome P-450 Enzyme System, pubmed-meshheading:15308663-Databases as Topic, pubmed-meshheading:15308663-Drosophila, pubmed-meshheading:15308663-Gene Expression Regulation, pubmed-meshheading:15308663-Glutathione Transferase, pubmed-meshheading:15308663-Longevity, pubmed-meshheading:15308663-Models, Biological, pubmed-meshheading:15308663-Models, Chemical, pubmed-meshheading:15308663-Mutation, pubmed-meshheading:15308663-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:15308663-Oligonucleotides, pubmed-meshheading:15308663-Promoter Regions, Genetic, pubmed-meshheading:15308663-RNA, pubmed-meshheading:15308663-Receptor, Insulin, pubmed-meshheading:15308663-Signal Transduction, pubmed-meshheading:15308663-Time Factors, pubmed-meshheading:15308663-Transcription, Genetic, pubmed-meshheading:15308663-Transcription Factors, pubmed-meshheading:15308663-Up-Regulation
pubmed:year
2004
pubmed:articleTitle
Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance.
pubmed:affiliation
Department of Biology, University College London, WC1E 6BT, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't