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Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression
We show that elevation of mitochondrial superoxide generation increases Caenorhabditis elegans life span by enhancing a RAS-dependent ROS (reactive oxygen species) signaling pathway (RDRS) that controls the expression of half of the genome as well as animal composition and physiology. RDRS stimulati...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710873/ https://www.ncbi.nlm.nih.gov/pubmed/36449615 http://dx.doi.org/10.1126/sciadv.adc9851 |
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author | Branicky, Robyn Wang, Ying Khaki, Arman Liu, Ju-Ling Kramer-Drauberg, Maximilian Hekimi, Siegfried |
author_facet | Branicky, Robyn Wang, Ying Khaki, Arman Liu, Ju-Ling Kramer-Drauberg, Maximilian Hekimi, Siegfried |
author_sort | Branicky, Robyn |
collection | PubMed |
description | We show that elevation of mitochondrial superoxide generation increases Caenorhabditis elegans life span by enhancing a RAS-dependent ROS (reactive oxygen species) signaling pathway (RDRS) that controls the expression of half of the genome as well as animal composition and physiology. RDRS stimulation mimics a program of change in gene expression that is normally observed at the end of postembryonic development. We further show that RDRS is regulated by negative feedback from the superoxide dismutase 1 (SOD-1)-dependent conversion of superoxide into cytoplasmic hydrogen peroxide, which, in turn, acts on a redox-sensitive cysteine (C118) of RAS. Preventing C118 oxidation by replacement with serine, or mimicking oxidation by replacement with aspartic acid, leads to opposite changes in the expression of the same large set of genes that is affected when RDRS is stimulated by mitochondrial superoxide. The identities of these genes suggest that stimulation of the pathway extends life span by boosting turnover and repair while moderating damage from metabolic activity. |
format | Online Article Text |
id | pubmed-9710873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97108732022-12-07 Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression Branicky, Robyn Wang, Ying Khaki, Arman Liu, Ju-Ling Kramer-Drauberg, Maximilian Hekimi, Siegfried Sci Adv Biomedicine and Life Sciences We show that elevation of mitochondrial superoxide generation increases Caenorhabditis elegans life span by enhancing a RAS-dependent ROS (reactive oxygen species) signaling pathway (RDRS) that controls the expression of half of the genome as well as animal composition and physiology. RDRS stimulation mimics a program of change in gene expression that is normally observed at the end of postembryonic development. We further show that RDRS is regulated by negative feedback from the superoxide dismutase 1 (SOD-1)-dependent conversion of superoxide into cytoplasmic hydrogen peroxide, which, in turn, acts on a redox-sensitive cysteine (C118) of RAS. Preventing C118 oxidation by replacement with serine, or mimicking oxidation by replacement with aspartic acid, leads to opposite changes in the expression of the same large set of genes that is affected when RDRS is stimulated by mitochondrial superoxide. The identities of these genes suggest that stimulation of the pathway extends life span by boosting turnover and repair while moderating damage from metabolic activity. American Association for the Advancement of Science 2022-11-30 /pmc/articles/PMC9710873/ /pubmed/36449615 http://dx.doi.org/10.1126/sciadv.adc9851 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Branicky, Robyn Wang, Ying Khaki, Arman Liu, Ju-Ling Kramer-Drauberg, Maximilian Hekimi, Siegfried Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title | Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title_full | Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title_fullStr | Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title_full_unstemmed | Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title_short | Stimulation of RAS-dependent ROS signaling extends longevity by modulating a developmental program of global gene expression |
title_sort | stimulation of ras-dependent ros signaling extends longevity by modulating a developmental program of global gene expression |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710873/ https://www.ncbi.nlm.nih.gov/pubmed/36449615 http://dx.doi.org/10.1126/sciadv.adc9851 |
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