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Hypoxia extends lifespan and neurological function in a mouse model of aging
There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies. Here, we asked whether chronic continuous hypoxia is beneficial i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204955/ https://www.ncbi.nlm.nih.gov/pubmed/37220109 http://dx.doi.org/10.1371/journal.pbio.3002117 |
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author | Rogers, Robert S. Wang, Hong Durham, Timothy J. Stefely, Jonathan A. Owiti, Norah A. Markhard, Andrew L. Sandler, Lev To, Tsz-Leung Mootha, Vamsi K. |
author_facet | Rogers, Robert S. Wang, Hong Durham, Timothy J. Stefely, Jonathan A. Owiti, Norah A. Markhard, Andrew L. Sandler, Lev To, Tsz-Leung Mootha, Vamsi K. |
author_sort | Rogers, Robert S. |
collection | PubMed |
description | There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies. Here, we asked whether chronic continuous hypoxia is beneficial in mammalian aging. We utilized the Ercc1 Δ/- mouse model of accelerated aging given that these mice are born developmentally normal but exhibit anatomic, physiological, and biochemical features of aging across multiple organs. Importantly, they exhibit a shortened lifespan that is extended by dietary restriction, the most potent aging intervention across many organisms. We report that chronic continuous 11% oxygen commenced at 4 weeks of age extends lifespan by 50% and delays the onset of neurological debility in Ercc1 Δ/- mice. Chronic continuous hypoxia did not impact food intake and did not significantly affect markers of DNA damage or senescence, suggesting that hypoxia did not simply alleviate the proximal effects of the Ercc1 mutation, but rather acted downstream via unknown mechanisms. To the best of our knowledge, this is the first study to demonstrate that “oxygen restriction” can extend lifespan in a mammalian model of aging. |
format | Online Article Text |
id | pubmed-10204955 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-102049552023-05-24 Hypoxia extends lifespan and neurological function in a mouse model of aging Rogers, Robert S. Wang, Hong Durham, Timothy J. Stefely, Jonathan A. Owiti, Norah A. Markhard, Andrew L. Sandler, Lev To, Tsz-Leung Mootha, Vamsi K. PLoS Biol Short Reports There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies. Here, we asked whether chronic continuous hypoxia is beneficial in mammalian aging. We utilized the Ercc1 Δ/- mouse model of accelerated aging given that these mice are born developmentally normal but exhibit anatomic, physiological, and biochemical features of aging across multiple organs. Importantly, they exhibit a shortened lifespan that is extended by dietary restriction, the most potent aging intervention across many organisms. We report that chronic continuous 11% oxygen commenced at 4 weeks of age extends lifespan by 50% and delays the onset of neurological debility in Ercc1 Δ/- mice. Chronic continuous hypoxia did not impact food intake and did not significantly affect markers of DNA damage or senescence, suggesting that hypoxia did not simply alleviate the proximal effects of the Ercc1 mutation, but rather acted downstream via unknown mechanisms. To the best of our knowledge, this is the first study to demonstrate that “oxygen restriction” can extend lifespan in a mammalian model of aging. Public Library of Science 2023-05-23 /pmc/articles/PMC10204955/ /pubmed/37220109 http://dx.doi.org/10.1371/journal.pbio.3002117 Text en © 2023 Rogers et al 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 author and source are credited. |
spellingShingle | Short Reports Rogers, Robert S. Wang, Hong Durham, Timothy J. Stefely, Jonathan A. Owiti, Norah A. Markhard, Andrew L. Sandler, Lev To, Tsz-Leung Mootha, Vamsi K. Hypoxia extends lifespan and neurological function in a mouse model of aging |
title | Hypoxia extends lifespan and neurological function in a mouse model of aging |
title_full | Hypoxia extends lifespan and neurological function in a mouse model of aging |
title_fullStr | Hypoxia extends lifespan and neurological function in a mouse model of aging |
title_full_unstemmed | Hypoxia extends lifespan and neurological function in a mouse model of aging |
title_short | Hypoxia extends lifespan and neurological function in a mouse model of aging |
title_sort | hypoxia extends lifespan and neurological function in a mouse model of aging |
topic | Short Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204955/ https://www.ncbi.nlm.nih.gov/pubmed/37220109 http://dx.doi.org/10.1371/journal.pbio.3002117 |
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