Roles of hypoxia-inducible factor-prolyl hydroxylases in aging and disease.
Abstract
The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on hypoxia, there is a growing recognition of its importance under normoxic conditions. Recent advances in PHD biology have highlighted the potential of targeting this pathway therapeutically for a range of aging-related diseases. In this article, we review these recent discoveries, situate them within the broader context of aging and disease, and explore current therapeutic strategies that target PHD enzymes for these indications.
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Research summary
The paper discusses the role of hypoxia-inducible factor-prolyl hydroxylases (HIF-PH) in aging and disease, highlighting their potential therapeutic targeting for aging-related diseases. This aligns with the exploration of mechanisms that could address root causes of aging rather than merely treating symptoms. However, while the findings are solid and contribute to the understanding of the HIF-PH signaling axis, the impact appears limited in scope, focusing on a specific pathway without presenting groundbreaking insights that could significantly advance the field of longevity research.
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