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Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity
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| Zeitschriftentitel: | Aging Cell |
|---|---|
| Personen und Körperschaften: | , , , |
| In: | Aging Cell, 9, 2010, 4, S. 636-646 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore |
|---|---|
| author |
Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore |
| spellingShingle |
Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore Aging Cell Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity Cell Biology Aging |
| author_sort |
spanier, britta |
| spelling |
Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore 1474-9718 1474-9726 Wiley Cell Biology Aging http://dx.doi.org/10.1111/j.1474-9726.2010.00591.x <jats:title>Summary</jats:title><jats:p>The insulin‐like signalling pathway is a central regulator of development, metabolism, stress resistance and lifespan in eukaryotes. <jats:italic>Caenorhabditis elegans daf‐2(e1370)</jats:italic> 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 <jats:italic>pept‐1</jats:italic> further increases lifespan by 60%. In assessing the underlying molecular mechanisms for this phenomenon, microarray‐based transcriptome data sets of <jats:italic>daf‐2(e1370)</jats:italic> and <jats:italic>daf‐2(e1370);pept‐1(lg601)</jats:italic> animals were compared with a focus on genes that showed significantly higher changes in expression levels in <jats:italic>daf‐2;pept‐1</jats:italic> than in <jats:italic>daf‐2</jats:italic>. 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 <jats:italic>daf‐2;pept‐1</jats:italic> with a strict dependance on DAF‐16. Loss of DAF‐9/DAF‐12 or KRI‐1 reduces the lifespan of <jats:italic>daf‐2;pept‐1</jats:italic> to that of the <jats:italic>daf‐2</jats:italic> mutant. Amongst the DAF‐16 target genes, numerous enzymes involved in the defence of reactive oxygen species were with increased expression level in <jats:italic>daf‐2;pept‐1</jats:italic>. On a functional level, it was demonstrated that amongst those, a high <jats:italic>de novo</jats:italic> 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 <jats:italic>C. elegans</jats:italic> lacking a proper function of the insulin receptor and lacking the intestinal peptide transporter.</jats:p> Altered signalling from germline to intestine pushes <i>daf‐2;pept‐1 Caenorhabditis elegans</i> into extreme longevity Aging Cell |
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Wiley, 2010 |
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| title |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_unstemmed |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_full |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_fullStr |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_full_unstemmed |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_short |
Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_sort |
altered signalling from germline to intestine pushes <i>daf‐2;pept‐1 caenorhabditis elegans</i> into extreme longevity |
| topic |
Cell Biology Aging |
| url |
http://dx.doi.org/10.1111/j.1474-9726.2010.00591.x |
| publishDate |
2010 |
| physical |
636-646 |
| description |
<jats:title>Summary</jats:title><jats:p>The insulin‐like signalling pathway is a central regulator of development, metabolism, stress resistance and lifespan in eukaryotes. <jats:italic>Caenorhabditis elegans daf‐2(e1370)</jats:italic> 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 <jats:italic>pept‐1</jats:italic> further increases lifespan by 60%. In assessing the underlying molecular mechanisms for this phenomenon, microarray‐based transcriptome data sets of <jats:italic>daf‐2(e1370)</jats:italic> and <jats:italic>daf‐2(e1370);pept‐1(lg601)</jats:italic> animals were compared with a focus on genes that showed significantly higher changes in expression levels in <jats:italic>daf‐2;pept‐1</jats:italic> than in <jats:italic>daf‐2</jats:italic>. 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 <jats:italic>daf‐2;pept‐1</jats:italic> with a strict dependance on DAF‐16. Loss of DAF‐9/DAF‐12 or KRI‐1 reduces the lifespan of <jats:italic>daf‐2;pept‐1</jats:italic> to that of the <jats:italic>daf‐2</jats:italic> mutant. Amongst the DAF‐16 target genes, numerous enzymes involved in the defence of reactive oxygen species were with increased expression level in <jats:italic>daf‐2;pept‐1</jats:italic>. On a functional level, it was demonstrated that amongst those, a high <jats:italic>de novo</jats:italic> 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 <jats:italic>C. elegans</jats:italic> lacking a proper function of the insulin receptor and lacking the intestinal peptide transporter.</jats:p> |
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| author | Spanier, Britta, Rubio‐Aliaga, Isabel, Hu, Hao, Daniel, Hannelore |
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| description | <jats:title>Summary</jats:title><jats:p>The insulin‐like signalling pathway is a central regulator of development, metabolism, stress resistance and lifespan in eukaryotes. <jats:italic>Caenorhabditis elegans daf‐2(e1370)</jats:italic> 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 <jats:italic>pept‐1</jats:italic> further increases lifespan by 60%. In assessing the underlying molecular mechanisms for this phenomenon, microarray‐based transcriptome data sets of <jats:italic>daf‐2(e1370)</jats:italic> and <jats:italic>daf‐2(e1370);pept‐1(lg601)</jats:italic> animals were compared with a focus on genes that showed significantly higher changes in expression levels in <jats:italic>daf‐2;pept‐1</jats:italic> than in <jats:italic>daf‐2</jats:italic>. 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 <jats:italic>daf‐2;pept‐1</jats:italic> with a strict dependance on DAF‐16. Loss of DAF‐9/DAF‐12 or KRI‐1 reduces the lifespan of <jats:italic>daf‐2;pept‐1</jats:italic> to that of the <jats:italic>daf‐2</jats:italic> mutant. Amongst the DAF‐16 target genes, numerous enzymes involved in the defence of reactive oxygen species were with increased expression level in <jats:italic>daf‐2;pept‐1</jats:italic>. On a functional level, it was demonstrated that amongst those, a high <jats:italic>de novo</jats:italic> 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 <jats:italic>C. elegans</jats:italic> lacking a proper function of the insulin receptor and lacking the intestinal peptide transporter.</jats:p> |
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| imprint | Wiley, 2010 |
| imprint_str_mv | Wiley, 2010 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
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| spelling | Spanier, Britta Rubio‐Aliaga, Isabel Hu, Hao Daniel, Hannelore 1474-9718 1474-9726 Wiley Cell Biology Aging http://dx.doi.org/10.1111/j.1474-9726.2010.00591.x <jats:title>Summary</jats:title><jats:p>The insulin‐like signalling pathway is a central regulator of development, metabolism, stress resistance and lifespan in eukaryotes. <jats:italic>Caenorhabditis elegans daf‐2(e1370)</jats:italic> 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 <jats:italic>pept‐1</jats:italic> further increases lifespan by 60%. In assessing the underlying molecular mechanisms for this phenomenon, microarray‐based transcriptome data sets of <jats:italic>daf‐2(e1370)</jats:italic> and <jats:italic>daf‐2(e1370);pept‐1(lg601)</jats:italic> animals were compared with a focus on genes that showed significantly higher changes in expression levels in <jats:italic>daf‐2;pept‐1</jats:italic> than in <jats:italic>daf‐2</jats:italic>. 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 <jats:italic>daf‐2;pept‐1</jats:italic> with a strict dependance on DAF‐16. Loss of DAF‐9/DAF‐12 or KRI‐1 reduces the lifespan of <jats:italic>daf‐2;pept‐1</jats:italic> to that of the <jats:italic>daf‐2</jats:italic> mutant. Amongst the DAF‐16 target genes, numerous enzymes involved in the defence of reactive oxygen species were with increased expression level in <jats:italic>daf‐2;pept‐1</jats:italic>. On a functional level, it was demonstrated that amongst those, a high <jats:italic>de novo</jats:italic> 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 <jats:italic>C. elegans</jats:italic> lacking a proper function of the insulin receptor and lacking the intestinal peptide transporter.</jats:p> Altered signalling from germline to intestine pushes <i>daf‐2;pept‐1 Caenorhabditis elegans</i> into extreme longevity Aging Cell |
| spellingShingle | Spanier, Britta, Rubio‐Aliaga, Isabel, Hu, Hao, Daniel, Hannelore, Aging Cell, Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity, Cell Biology, Aging |
| title | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_full | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_fullStr | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_full_unstemmed | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_short | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| title_sort | altered signalling from germline to intestine pushes <i>daf‐2;pept‐1 caenorhabditis elegans</i> into extreme longevity |
| title_unstemmed | Altered signalling from germline to intestine pushes daf‐2;pept‐1 Caenorhabditis elegans into extreme longevity |
| topic | Cell Biology, Aging |
| url | http://dx.doi.org/10.1111/j.1474-9726.2010.00591.x |