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Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans
Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unkno...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116436/ https://www.ncbi.nlm.nih.gov/pubmed/24889782 http://dx.doi.org/10.1111/acel.12232 |
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author | Lin, Yen-Hung Chen, Yi-Chun Kao, Tzu-Yu Lin, Yi-Chun Hsu, Tzu-En Wu, Yi-Chun Ja, William W Brummel, Theodore J Kapahi, Pankaj Yuh, Chiou-Hwa Yu, Lin-Kwei Lin, Zhi-Han You, Ru-Jing Jhong, Yi-Ting Wang, Horng-Dar |
author_facet | Lin, Yen-Hung Chen, Yi-Chun Kao, Tzu-Yu Lin, Yi-Chun Hsu, Tzu-En Wu, Yi-Chun Ja, William W Brummel, Theodore J Kapahi, Pankaj Yuh, Chiou-Hwa Yu, Lin-Kwei Lin, Zhi-Han You, Ru-Jing Jhong, Yi-Ting Wang, Horng-Dar |
author_sort | Lin, Yen-Hung |
collection | PubMed |
description | Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging. |
format | Online Article Text |
id | pubmed-4116436 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-41164362015-02-19 Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans Lin, Yen-Hung Chen, Yi-Chun Kao, Tzu-Yu Lin, Yi-Chun Hsu, Tzu-En Wu, Yi-Chun Ja, William W Brummel, Theodore J Kapahi, Pankaj Yuh, Chiou-Hwa Yu, Lin-Kwei Lin, Zhi-Han You, Ru-Jing Jhong, Yi-Ting Wang, Horng-Dar Aging Cell Original Articles Target of rapamycin (TOR) signaling is a nutrient-sensing pathway controlling metabolism and lifespan. Although TOR signaling can be activated by a metabolite of diacylglycerol (DAG), phosphatidic acid (PA), the precise genetic mechanism through which DAG metabolism influences lifespan remains unknown. DAG is metabolized to either PA via the action of DAG kinase or 2-arachidonoyl-sn-glycerol by diacylglycerol lipase (DAGL). Here, we report that in Drosophila and Caenorhabditis elegans, overexpression of diacylglycerol lipase (DAGL/inaE/dagl-1) or knockdown of diacylglycerol kinase (DGK/rdgA/dgk-5) extends lifespan and enhances response to oxidative stress. Phosphorylated S6 kinase (p-S6K) levels are reduced following these manipulations, implying the involvement of TOR signaling. Conversely, DAGL/inaE/dagl-1 mutants exhibit shortened lifespan, reduced tolerance to oxidative stress, and elevated levels of p-S6K. Additional results from genetic interaction studies are consistent with the hypothesis that DAG metabolism interacts with TOR and S6K signaling to affect longevity and oxidative stress resistance. These findings highlight conserved metabolic and genetic pathways that regulate aging. BlackWell Publishing Ltd 2014-08 2014-05-30 /pmc/articles/PMC4116436/ /pubmed/24889782 http://dx.doi.org/10.1111/acel.12232 Text en © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Lin, Yen-Hung Chen, Yi-Chun Kao, Tzu-Yu Lin, Yi-Chun Hsu, Tzu-En Wu, Yi-Chun Ja, William W Brummel, Theodore J Kapahi, Pankaj Yuh, Chiou-Hwa Yu, Lin-Kwei Lin, Zhi-Han You, Ru-Jing Jhong, Yi-Ting Wang, Horng-Dar Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title | Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title_full | Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title_fullStr | Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title_full_unstemmed | Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title_short | Diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating TOR signaling in Drosophila and C. elegans |
title_sort | diacylglycerol lipase regulates lifespan and oxidative stress response by inversely modulating tor signaling in drosophila and c. elegans |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4116436/ https://www.ncbi.nlm.nih.gov/pubmed/24889782 http://dx.doi.org/10.1111/acel.12232 |
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