Academic Journal
Oxygenaging: A Physiological Framework for Geroscience.
| Τίτλος: | Oxygenaging: A Physiological Framework for Geroscience. |
|---|---|
| Συγγραφείς: | Donega S; Translational Gerontology Branch (TGB), National Institute on Aging (NIA), Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA., Fishbein KW; Laboratory of Clinical Investigation (LCI), NIA, IRP, NIH, Baltimore, Maryland, USA., Dominelli P; Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada., Herman AB; Laboratory of Cardiovascular Science (LCS), NIA, IRP, NIH, Baltimore, Maryland, USA., de Cabo R; Translational Gerontology Branch (TGB), National Institute on Aging (NIA), Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA., Gorospe M; Laboratory of Genetics and Genomics (LGG), NIA, IRP, NIH, Baltimore, Maryland, USA., Ferrucci L; Translational Gerontology Branch (TGB), National Institute on Aging (NIA), Intramural Research Program (IRP), National Institutes of Health (NIH), Baltimore, Maryland, USA. |
| Πηγή: | Aging cell [Aging Cell] 2026 Sep; Vol. 25 (9), pp. e70664. |
| Τύπος έκδοσης: | Journal Article; Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Wiley-Blackwell Original Publication: Oxford, UK : Blackwell Pub., c2002- |
| Ιατρικοί όροι (MeSH): | Oxygen*/metabolism , Aging*/metabolism , Aging*/physiology , Geroscience*/methods, Mitochondria/metabolism ; Humans ; Animals ; Oxidative Stress |
| Περίληψη: | The stepwise movement of oxygen from the atmosphere to the mitochondria, the "oxygen cascade", is one of the most tightly regulated systems in physiology. Despite decades of mechanistic study, it has remained quite unexplored in Geroscience. This oversight should be reconsidered. In young organisms, hypoxic stress (whether environmental or tissue-specific) activates a complex adaptive response to preserve energetic stability via restraining anabolic pathways, optimizing mitochondrial performance, and reinforcing cellular quality control systems. With advancing age, angiostatic signaling increases, endothelial metabolism becomes dysregulated, and overall alveolar ventilation and pulmonary gas exchange (ventilation-perfusion matching and diffusion capacity) become less efficient. These changes promote microvascular rarefaction and low-grade but persistent mismatches between oxygen delivery and demand at the tissue level, ultimately destabilizing cellular function. In this review, we propose that the gradual erosion of oxygen homeostasis is not simply a byproduct of aging, but also a driver of molecular damage and functional decline. We examine the aging oxygen cascade through the framework of resilience biology, focusing on mechanisms such as mitochondrial electron leaks, oxidative stress amplification, iron dyshomeostasis, ferroptosis, and epigenetic remodeling. We also discuss interventions that alter oxygen availability, such as intermittent hypoxia, hyperbaric oxygen therapy, and hypoxic-hyperoxic training. These approaches demonstrate adaptive potential, but they also highlight the narrow margin between beneficial stress and injury. We propose "Oxygenaging" as a unifying framework in which aging associates with the progressive loss of equilibrium across the oxygen cascade, linking systemic oxygen transport to mitochondrial function, genomic stability, and cellular resilience. (© 2026 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.) |
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| Contributed Indexing: | Keywords: Oxygenaging; RNA splicing; aging; energy; epigenetics; hyperoxia; hypoxia; hypoxia inducible factor 1 (HIF1); mitochondria; oxygen |
| Substance Nomenclature: | S88TT14065 (Oxygen) |
| Entry Date(s): | Date Created: 20260828 Date Completed: 20260828 Latest Revision: 20260830 |
| Update Code: | 20260830 |
| PubMed Central ID: | PMC13523615 |
| DOI: | 10.1111/acel.70664 |
| PMID: | 42663406 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1474-9726 |
|---|---|
| DOI: | 10.1111/acel.70664 |