Fedor Galkin , Fadi E. Pulous , Yanyun Fu , Man Zhang , Frank W. Pun , Feng Ren , Alex Zhavoronkov
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Roles of hypoxia-inducible factor-prolyl hydroxylases in aging and disease
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.
期刊介绍：
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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