Understanding Human Aging and the Fundamental Cell Signaling Link in Age-Related Diseases: The Middle-Aging Hypovascularity Hypoxia Hypothesis

    June 2023 in “ Frontiers in Aging ”
    Teow J. Phua
    TLDR Improving blood flow and oxygen levels in middle age may help prevent age-related diseases.
    The document explores the "middle-aging hypovascularity hypoxia hypothesis," which links age-related diseases to decreased vascularity and oxygenation during middle age. It emphasizes the role of hormonal signaling, particularly testosterone and estrogen, in reversing hypovascularity, and the impact of nitric oxide (NO) signaling on endothelial dysfunction. The hypothesis suggests that maintaining NO bioavailability through pathways like NO-cGMP could improve vasodilation and tissue oxygenation, potentially mitigating diseases such as type 2 diabetes, heart failure, and dementia. The review also discusses the testosterone–vascular–inflamm-aging triad, noting that declining testosterone levels can lead to vascular aging. It highlights the potential of PDE5 inhibitors and supplements like L-arginine and curcumin to improve vascular function. The document underscores the importance of understanding oxygen homeostasis and the role of hypoxia-inducible factor (HIF) in protecting against neurodegeneration, while also exploring translational imaging technologies to assess microcirculation changes related to aging.
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