Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans.

TitleGenes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans.
Publication TypeJournal Article
Year of Publication2003
AuthorsMurphy CT, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C
JournalNature
Volume424
Issue6946
Pagination277-83
Date Published2003 Jul 17
ISSN1476-4687
KeywordsAging, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cluster Analysis, Feedback, Physiological, Forkhead Transcription Factors, Gene Expression Regulation, Developmental, Genes, Helminth, Insulin, Insulin-Like Growth Factor I, Longevity, Oligonucleotide Array Sequence Analysis, Receptor, Insulin, Response Elements, RNA Interference, RNA, Helminth, Signal Transduction, Stress, Physiological, Time Factors, Transcription Factors, Transcription, Genetic
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.

DOI10.1038/nature01789
Alternate JournalNature
PubMed ID12845331
Grant List054523 / / Wellcome Trust / United Kingdom