Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
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
_version_ 1785045937872175104
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
work_keys_str_mv AT rogersroberts hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT wanghong hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT durhamtimothyj hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT stefelyjonathana hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT owitinoraha hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT markhardandrewl hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT sandlerlev hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT totszleung hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging
AT moothavamsik hypoxiaextendslifespanandneurologicalfunctioninamousemodelofaging