<p>Reactive Oxygen Species: Drivers of Physiological and Pathological Processes</p>

Journal of Inflammation Research, Год журнала: 2020, Номер Volume 13, С. 1057 - 1073

Опубликована: Дек. 1, 2020

Abstract: Since the Great Oxidation Event, about 2.4 billion years ago, Earth is immersed in an oxidizing atmosphere. Thus, it has been proposed that excess oxygen, originally a waste product of photosynthetic cyanobacteria, induced oxidative stress and production reactive oxygen species (ROS), which have since acted as fundamental drivers biologic evolution eukaryogenesis. Indeed, throughout organism's lifespan, ROS affect directly (as mutagens) or indirectly messengers regulators) all structural functional components cells, many aspects cell biology. Whether left unchecked by protective antioxidant systems, not only cause genomic mutations but also induce irreversible modification proteins (protein oxidation peroxidation), lipids glycans (advanced lipoxidation glycation end products), impairing their function promoting disease death. Conversely, low-level local play important role both redox-signaling molecules wide spectrum pathways involved maintenance cellular homeostasis (MAPK/ERK, PTK/PTP, PI3K-AKT-mTOR), regulating key transcription factors (NFκB/IκB, Nrf2/KEAP1, AP-1, p53, HIF-1). Consequently, can shape variety functions, including proliferation, differentiation, migration apoptosis. In this review, we will give brief overview relevance physiological pathological processes, particularly inflammation aging. In-depth knowledge molecular mechanisms actuation influence under steady-state stressful conditions pave way for development novel therapeutic interventions. This mitigate harmful outcomes onset progression chronic inflammatory age-related diseases. Keywords: species, stress,

Язык: Английский

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A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Авг. 16, 2022

Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment bone biopsies from two aged human cohorts. We further demonstrate reductions SenMayo following genetic clearance of cells mice adipose tissue humans pharmacological clearance. next use to identify hematopoietic or mesenchymal at single level murine marrow/bone scRNA-seq data. Thus, identifies across tissues species with high fidelity. Using this panel, are able characterize key intercellular signaling pathways. also represents potentially clinically applicable panel for monitoring burden aging other conditions as well studies senolytic drugs.

Язык: Английский

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Senolytics and senomorphics: Natural and synthetic therapeutics in the treatment of aging and chronic diseases

Free Radical Biology and Medicine, Год журнала: 2021, Номер 171, С. 169 - 190

Опубликована: Май 12, 2021

Язык: Английский

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AGE/RAGE in diabetic kidney disease and ageing kidney

Free Radical Biology and Medicine, Год журнала: 2021, Номер 171, С. 260 - 271

Опубликована: Май 18, 2021

Язык: Английский

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SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress

Frontiers in Physiology, Год журнала: 2021, Номер 11

Опубликована: Янв. 15, 2021

Endothelial cells have emerged as key players in SARS-CoV-2 infection and COVID-19 inflammatory pathologies. Dysfunctional endothelial can promote chronic inflammation disease processes like thrombosis, atherosclerosis, lung injury. In cells, mitochondria regulate these pathways via redox signaling, which is primarily achieved through mitochondrial reactive oxygen species (mtROS). Excess mtROS causes oxidative stress that initiate exacerbate senescence, a state promotes dysfunction. Oxidative also activate feedback loops perpetuate dysfunction, overproduction, inflammation. this review, we provide an overview of phenotypes mediated by - such inflammation, senescence well how states may be initiated cells. We propose activates mtROS-mediated cause long-term changes host status function, promoting cardiovascular injury after recovery from COVID-19. Finally, discuss the implications proposed on vascular health potential treatments to address conditions.

Язык: Английский

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Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies

Pharmacological Reviews, Год журнала: 2023, Номер 75(4), С. 675 - 713

Опубликована: Фев. 2, 2023

An increase in life expectancy developed countries has led to a surge of chronic aging-related diseases. In the last few decades, several studies have provided evidence prominent role cellular senescence many these pathologies. Key traits senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift senescence-associated secretory phenotype resulting increased secretion various intermediate bioactive factors important for pathophysiology. However, is highly phenotypically heterogeneous process, hindering discovery totally specific accurate biomarkers. Also, strategies prevent pathologic effect accumulation during aging by impairing onset or promoting clearance shown great potential vivo studies, some are already early stages clinical translation. The adaptability senotherapeutic approaches human application been questioned due lack proper targeting involvement physiologic functions. this review, we explore its influence on expression biomarkers currently used detection. We also discuss current regarding efficacy, reliability, development stage, applicability main existing strategies.

Significance Statement

This paper an extensive review what known about complex process explores most defining features. body discussion focuses how multifeature fluctuation physiological both caused limitation search truly reliable progression senotherapies.

Язык: Английский

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Novel insights into ferroptosis: Implications for age-related diseases

Theranostics, Год журнала: 2020, Номер 10(26), С. 11976 - 11997

Опубликована: Янв. 1, 2020

Rapid increase in aging populations is an urgent problem because older adults are more likely to suffer from disabilities and age-related diseases (ARDs), burdening healthcare systems society general. ARDs characterized by the progressive deterioration of tissues organs over time, eventually leading tissue organ failure. To date, there no effective interventions prevent progression ARDs. Hence, need for new treatment strategies. Ferroptosis, iron-dependent cell death, linked normal development homeostasis. Accumulating evidence, however, has highlighted crucial roles ferroptosis ARDs, including neurodegenerative cardiovascular diseases. In this review, we a) summarize initiation, regulatory mechanisms, molecular signaling pathways involved ferroptosis, b) discuss direct indirect involvement activation and/or inhibition pathogenesis some important diseases, c) highlight therapeutic targets relevant

Язык: Английский

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Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics

Antioxidants, Год журнала: 2023, Номер 12(2), С. 444 - 444

Опубликована: Фев. 10, 2023

Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and increased probability of death. Cellular senescence has been typically considered as anti-proliferative process; however, the chronic accumulation senescent cells contributes tissue dysfunction aging. In this review, we discuss some most important hallmarks biomarkers cellular with special focus on skin biomarkers, reactive oxygen species (ROS), senotherapeutic strategies eliminate or prevent senescence. Although them are not exclusive senescence, expression senescence-associated beta-galactosidase (SA-β-gal) enzyme seems be reliable biomarker for distinguishing from those arrested cell cycle. The presence stable DNA damage response (DDR) secretory phenotype (SASP) mediators ROS representative Senotherapeutics based natural compounds such quercetin, naringenin, apigenin have shown promising results regarding SASP reduction. These seem cells, likely through inhibition pro-survival signaling pathways. studies still required verify their short- long-term effects, these therapies may effective strategy

Язык: Английский

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Molecular Mechanisms of Cellular Senescence in Neurodegenerative Diseases

Journal of Molecular Biology, Год журнала: 2023, Номер 435(12), С. 168114 - 168114

Опубликована: Апрель 20, 2023

Язык: Английский

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Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies

Aging and Disease, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Cellular senescence is characterized by the permanent arrest of cell proliferation and a response to endogenous exogenous stress. The continuous accumulation senescent cells (SnCs) in body leads development aging age-related diseases (such as neurodegenerative diseases, cancer, metabolic cardiovascular osteoarthritis). In face growing challenge several compounds have received widespread attention for their potential target SnCs. As result, senolytics (compounds that selectively eliminate SnCs) senomorphics alter intercellular communication modulate behavior become hot research topics field anti-aging. addition, strategies such combination therapies immune-based approaches also made significant progress anti-aging therapy. this article, we discuss latest on targeting SnCs gain deeper understanding mechanism action impact different with aim providing more effective references therapeutic ideas clinical treatment ever-grave challenges diseases.

Язык: Английский

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