TY - JOUR
T1 - Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans
AU - Murphy, Coleen T.
AU - McCarroll, Steven A.
AU - Bargmann, Cornelia I.
AU - Fraser, Andrew
AU - Kamath, Ravi S.
AU - Ahringer, Julie
AU - Li, Hao
AU - Kenyon, Cynthia
PY - 2003/7/17
Y1 - 2003/7/17
N2 - 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.
AB - 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.
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U2 - 10.1038/nature01789
DO - 10.1038/nature01789
M3 - Article
C2 - 12845331
AN - SCOPUS:0042092531
SN - 0028-0836
VL - 424
SP - 277
EP - 284
JO - Nature
JF - Nature
IS - 6946
ER -