Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 15, 2024

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, critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, epigenetic modifications. This review explores interconnected roles hypoxia in aging, highlighting how hypoxic conditions exacerbate damage, promote senescence, contribute age‐related pathologies, including cardiovascular neurodegenerative disorders, cancer, metabolic dysfunctions, pulmonary conditions. By examining mechanisms linking we identify key serve potential therapeutic targets. Emerging interventions such HIF modulators, antioxidants, senolytics, lifestyle modifications hold promise mitigating adverse effects on tissues. However, challenges heterogeneity lack reliable biomarkers, safety concerns regarding hypoxia‐targeted therapies remain. emphasizes need for personalized approaches advanced technologies develop effective antiaging interventions. integrating current knowledge, this provides comprehensive framework underscores importance targeting hypoxia‐induced enhance healthy reduce burden diseases.

Language: Английский

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Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 248 - 248

Published: Feb. 26, 2025

Multiple sclerosis (MS) is an autoimmune disease that damages the myelin sheath around central nervous system axons, leading to neurological dysfunction. Although initial damage driven by inflammation, hypoxia has been reported in several brain regions of MS patients, but significance this for prognosis and treatment remains unclear. Neuroinflammation can induce hypoxia, exacerbate neuroinflammation, forming a vicious cycle. Within lesions, demyelination often followed remyelination, which may restore function. However, demyelinated axons are vulnerable damage, leads accumulation permanent dysfunction typical MS, with vulnerability heightened during hypoxia. Clinically approved therapies immunomodulatory, reduce relapse frequency/severity, there lack pro-regenerative example promoting remyelination. All tissues have protective responses be relevant especially remyelinating episodes. When oxygen levels reduced brain, constitutively expressed hypoxia-inducible factors (HIF) stabilised, upregulating hundreds genes, including neuroprotective factors. Furthermore, astrocytes upregulate heparin-binding epidermal growth factor (EGF)-like (HB-EGF) early stage MS. HB-EGF promotes mechanisms induces oligodendrocyte neuron differentiation survival. This review article outlines neuroinflammation cycle pathology identifies potential therapeutic targets limit neurodegeneration and/or promote regeneration. Both HIF signalling pathways endogenous protection CNS, neuroprotection remyelination directly, also indirectly modulating immune response Promoting such could effective therapy patients.

Language: Английский

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Electroacupuncture ameliorates cognitive impairment and white matter injury in vascular dementia rats via activating HIF-1α/VEGF/VEGFR2 pathway

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Integrative Multi‐Omics and Routine Blood Analysis Using Deep Learning: Cost‐Effective Early Prediction of Chronic Disease Risks

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Chronic noncommunicable diseases (NCDS) are often characterized by gradual onset and slow progression, but the difficulty in early prediction remains a substantial health challenge worldwide. This study aims to explore interconnectedness of disease occurrence through multi-omics studies validate it large-scale electronic records. In response, research examined data from 160 sub-healthy individuals at high altitude then deep learning model called Omicsformer is developed for detailed analysis classification routine blood samples. adeptly identified potential risks nine including cancer, cardiovascular conditions, psychiatric conditions. Analysis risk trajectories 20 years large clinical patients confirmed validity group preclinical assessment, revealing trends increased time onset. Additionally, straightforward NCDs system developed, utilizing basic test results. work highlights role multiomics chronic risk, development validation predictive models based on results can help advance personalized medicine reduce cost screening community.

Language: Английский

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Endothelial -targeted CD39 is protective in a mouse model of global forebrain ischaemia

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 21, 2025

Abstract Global ischemic brain injury occurs after cardiac arrest or prolonged hypotensive episodes following surgery trauma. It causes significant neurological deficits even successful re-establishment of blood flow. is the primary cause death in 68% inpatient and 23% out-of-hospital cases, but there are currently no treatments. Endothelial activation dysfunction impairing small vessel flow damage. Purinergic signaling an endogenous molecular pathway, where CD39 CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia, eATP released, triggering thrombosis inflammation. In contrast, anti-thrombotic, protects against oxidative stress, suppresses immune response. Our group developed a bifunctional compound – anti-VCAM-CD39 that targets dysregulated endothelium promotes generation at infarct site, localising antithrombotic anti-inflammatory effects CD39. We investigated whether could improve outcome murine model global ischaemia caused by dual carotid artery ligation (DCAL). Test drugs controls were given 3 h 30 min ischaemia. Assessments 24 included function, volume, perfusion, albumin extravasation assess blood-brain barrier (BBB) permeability. showed was overall improvement deficit anti-VCAM-CD39-treated mice DCAL. MRI revealed these had significantly smaller infarcts reduced apoptotic activity on side permanent occlusion, compared saline treated mice. There DCAL, suggesting conferred neuroprotection through preservation BBB vitro findings confirmed anti-VCAM-CD39-mediated production protected hypoxia-induced endothelial cell death. novel therapeutic can promote neuroprotection, reduce tissue damage inflammation hypoxic These suggest be new avenue therapy potentially used other cerebrovascular diseases constant underlying pathology.

Language: Английский

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Urapidil as a neuroprotective agent: targeting hypoxia, inflammation, and oxidative stress in traumatic brain injury

European Journal of Trauma and Emergency Surgery, Journal Year: 2025, Volume and Issue: 51(1)

Published: May 6, 2025

Language: Английский

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Hypoxia Pathways in Parkinson’s Disease: From Pathogenesis to Therapeutic Targets

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10484 - 10484

Published: Sept. 29, 2024

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to can lead loss consciousness within seconds and death minutes. Recent studies have identified regions with spontaneous episodic hypoxia, referred as “hypoxic pockets”. Hypoxia also result from impaired blood flow due conditions such heart disease, clots, stroke, or hemorrhage, well reduced intake excessive consumption caused by factors like low ambient pulmonary diseases, infections, inflammation, cancer. Severe hypoxia in manifest symptoms similar Parkinson’s disease (PD), including cerebral edema, mood disturbances, cognitive impairments. Additionally, development PD appears be closely associated hypoxic pathways. This review seeks investigate molecular interactions between PD, emphasizing pathological role pathways exploring their potential therapeutic targets.

Language: Английский

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Molecular profiling of a rat model of vascular dementia: Evidences from proteomics, metabolomics and experimental validations

Brain Research, Journal Year: 2024, Volume and Issue: 1846, P. 149254 - 149254

Published: Sept. 26, 2024

Language: Английский

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Electrochemical sensing of transient ascorbate fluctuation under hypoxic stress in live rat brain

Talanta, Journal Year: 2024, Volume and Issue: 282, P. 126996 - 126996

Published: Oct. 5, 2024

Language: Английский

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Role of Hypoxia Induced by Medicinal Plants; A Revolutionary Era of Cellular and Molecular Herbal Medicine in Neuroblastoma Treatment

Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)

Published: Dec. 20, 2024

As one of the most common solid pediatric cancers, Neuroblastoma (NBL) accounts for 15% all cancer-related mortalities in infants with increasing incidence around world. Despite current therapeutic approaches NBL (radiotherapies, surgeries, and chemotherapies), these could not be beneficial patients due to their low effectiveness, some severe side effects. These challenges lead basic medical scientists clinical specialists toward an optimal interventions management NBL. Regardingly, taking molecular cellular immunopathophysiology involved hypoxic microenvironment into account, it can practically a contributing approach development "molecular medicine" treatment Interestingly, pivotal roles "herbal have been extensively interrogated treating NBL, functionally being served as anti-cancer agent via inducing wide range signaling, like apoptosis, cell cycle arrest, inhibiting angiogenesis. Hence, this review study, authors aim summarize anti-tumor effects medicinal plants phytoconstituents through immunopathophysiological mechanisms In addition, they try open promising windows immune gene-based therapies "precision advantages herbal medicine. An interdisciplinary collaboration among translation medicine specialists, immunobiologists, neuro-oncologists is highly recommended.

Language: Английский

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