Altered signalling from germline to intestine pushes daf-2;pept-1 Caenorhabditis elegans into extreme longevity.

Authors: Spanier B; Rubio-Aliaga I; Hu H; Daniel H

Abstract: The insulin-like signalling pathway is a central regulator of development, metabolism, stress resistance and lifespan in eukaryotes. Caenorhabditis elegans daf-2(e1370) animals with a loss-of-function mutation in the insulin-like receptor live twice as long as wild-type animals, and the additional knockout of the intestinal di- and tripeptide transporter pept-1 further increases lifespan by 60%. In assessing the underlying molecular mechanisms for this phenomenon, microarray-based transcriptome data sets of daf-2(e1370) and daf-2(e1370);pept-1(lg601) animals were compared with a focus on genes that showed significantly higher changes in expression levels in daf-2;pept-1 than in daf-2. We identified 187 genes with at least fourfold decreased transcript levels and 170 with more than a fourfold increase. A large fraction of the down-regulated genes encode proteins involved in germline proliferation and reproduction. The DAF-9/DAF-12 signalling cascade was identified as a prime pathway that mediates the longevity of daf-2;pept-1 with a strict dependance on DAF-16. Loss of DAF-9/DAF-12 or KRI-1 reduces the lifespan of daf-2;pept-1 to that of the daf-2 mutant. Amongst the DAF-16 target genes, numerous enzymes involved in the defence of reactive oxygen species were with increased expression level in daf-2;pept-1. On a functional level, it was demonstrated that amongst those, a high de novo synthesis rate of glutathione is most important for the longevity phenotype of this strain. Taken together, a close interdependence of endocrine hormone signalling from germline to intestine was identified as an essential element in the control of the extreme longevity of C. elegans lacking a proper function of the insulin receptor and lacking the intestinal peptide transporter.

Keywords: Animals; Caenorhabditis elegans/cytology/genetics/immunology/*physiology; Caenorhabditis elegans Proteins/*metabolism; Cell Proliferation; Down-Regulation/genetics; Genes, Helminth/genetics; Germ Cells/*metabolism; Glutathione/metabolism; Homeostasis; Intestines/*metabolism; Longevity/*physiology; Models, Biological; Mutation/genetics; RNA, Messenger/genetics/metabolism; Reactive Oxygen Species/metabolism; Receptor, Insulin/*metabolism; Reproduction/genetics; *Signal Transduction
Journal: Aging cell
Volume: 9
Issue: 4
Pages: 636-46
Date: June 17, 2010
PMID: 20550516
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Citation:

Spanier B, Rubio-Aliaga I, Hu H, Daniel H (2010) Altered signalling from germline to intestine pushes daf-2;pept-1 Caenorhabditis elegans into extreme longevity. Aging cell 9: 636-46.


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