Hypoxia extends lifespan and neurological function in a mouse model of aging
Name
journal.pbio.3002117.pdf
Description
Published version
Size
1.31 MB
Format
Adobe PDF
Checksum (MD5)
2f995079b339e8cda904b53ae80878b7
Author(s)
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
Date Issued
May 23, 2023
Journal
PLOS Biology
Publisher
Public Library of Science (PLoS)
Citation
Rogers RS, Wang H, Durham TJ, Stefely JA, Owiti NA, Markhard AL, et al. (2023) Hypoxia extends lifespan and neurological function in a mouse model of aging. PLoS Biol 21(5): e3002117.
Version
Final published version
Abstract
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.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pbio.3002117
