Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling.
In C. elegans, removing the germ cells extends life span by triggering the nuclear localization and activation of the DAF-16/FOXO transcription factor in the intestine. In this study, we identify and analyze genes required for germline removal to extend life span. We find that the reproductive system communicates with the intestine through lipophilic-hormone signaling and that a gene called kri-1 is likely to act in the intestine to promote DAF-16 nuclear localization in response to this signal. This lipophilic-signaling pathway and kri-1 are not required for DAF-16's nuclear localization and life-span extension in animals with decreased insulin/IGF-1 signaling. Thus, this pathway specifically enables the integration of cues from the reproductive system with central DAF-16-activation pathways to influence the aging of the animal.
Berman
Jennifer R
JR
Department of Biochemistry and Biophysics, Mission Bay Genentech Hall, 600 16th Street, Room S312D, University of California, San Francisco, San Francisco, CA 94143, USA.
Kenyon
Cynthia
C
D000375:Aging / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D051858:Forkhead Transcription Factors; D017930:Genes, Reporter; D005854:Germ Cells / Q000502:physiology*; D006728:Hormones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D000075927:KRIT1 Protein; D008136:Longevity / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014566:Urogenital System / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; C060620:Glp-1 protein, C elegans; D006728:Hormones; D007328:Insulin; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008562:Membrane Glycoproteins; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D051880:Receptors, Notch; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D051059:PTEN Phosphohydrolase