Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets
Ayesha Nisar,
Sawar Khan,
Wen Li,
Li Hu,
Priyadarshani Nadeeshika Samarawickrama,
Naheemat Modupeola Gold,
Meiting Zi,
Sardar Azhar Mehmood,
Jiarong Miao,
Yonghan He
Affiliations
Ayesha Nisar
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Sawar Khan
Department of Cell Biology, School of Life Sciences Central South University Changsha Hunan China
Wen Li
Department of Endocrinology The Second Affiliated Hospital of Dali University (the Third People's Hospital of Yunnan Province) Kunming Yunnan China
Li Hu
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Priyadarshani Nadeeshika Samarawickrama
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Naheemat Modupeola Gold
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Meiting Zi
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Sardar Azhar Mehmood
Department of Zoology Hazara University Mansehra Pakistan
Jiarong Miao
Department of Gastroenterology The First Affiliated Hospital of Kunming Medical University Kunming Yunnan China
Yonghan He
Key Laboratory of Genetic Evolution & Animal Models, KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan China
Abstract Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age‐related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia‐targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia‐induced pathways to enhance healthy aging and reduce the burden of age‐related diseases.
