Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling.

Authors: Berman JR; Kenyon C

Abstract: 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.

Keywords: Aging/*physiology; Animals; Animals, Genetically Modified; Caenorhabditis elegans/anatomy & histology/genetics/*physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Cell Nucleus/metabolism; Genes, Reporter; Germ Cells/*physiology; Hormones/chemistry/*metabolism; Humans; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; Intestines/metabolism; Longevity/*physiology; Membrane Glycoproteins/genetics/metabolism; Microtubule-Associated Proteins/genetics/metabolism; Models, Animal; Mutation; PTEN Phosphohydrolase/metabolism; Proto-Oncogene Proteins/genetics/metabolism; RNA Interference; Signal Transduction/*physiology; Transcription Factors/genetics/*metabolism; Urogenital System/metabolism
Journal: Cell
Volume: 124
Issue: 5
Pages: 1055-68
Date: March 15, 2006
PMID: 16530050
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Citation:

Berman JR, Kenyon C (2006) Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124: 1055-68.


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