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.
Murphy
Coleen T
CT
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-2200, USA.
McCarroll
Steven A
SA
Bargmann
Cornelia I
CI
Fraser
Andrew
A
Kamath
Ravi S
RS
Ahringer
Julie
J
Li
Hao
H
Kenyon
Cynthia
C
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D025461:Feedback, Physiological; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental; D017238:Genes, Helminth / Q000235:genetics* / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D018510:RNA, Helminth / Q000032:analysis / Q000235:genetics; D011972:Receptor, Insulin / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D018510:RNA, Helminth; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin