Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(10), P. 2499 - 2574

Published: Aug. 19, 2023

Abstract A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” characterized by low to mild levels oxidants involved in the regulation various biochemical transformations such carboxylation, hydroxylation, peroxidation, modulation signal transduction pathways Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related 2 (Nrf2) other processes. Increased ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result a harmful condition stress (“bad stress”). Although it widely accepted, that many chronic diseases are multifactorial origin, they share common denominator. Here we review importance mechanisms through which contributes pathological states an organism. Attention focused on chemistry ROS RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl nitric oxide, peroxynitrite), their role damage DNA, proteins, membrane lipids. Quantitative qualitative assessment biomarkers also discussed. Oxidative pathology cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s Parkinson’s Down syndrome), psychiatric (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, cancer), aging. The concerted action antioxidants ameliorate effect achieved antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), small molecular weight (vitamins C E, flavonoids, carotenoids, melatonin, ergothioneine, others). Perhaps one most effective vitamin first line defense against peroxidation promising approach appears be use flavonoids), showing weak prooxidant properties may boost cellular systems thus act preventive anticancer agents. Redox metal-based enzyme mimetic compounds potential pharmaceutical interventions sirtuins therapeutic targets for age-related anti-aging strategies

Language: Английский

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Aging Hallmarks and the Role of Oxidative Stress

Antioxidants, Journal Year: 2023, Volume and Issue: 12(3), P. 651 - 651

Published: March 6, 2023

Aging is a complex biological process accompanied by progressive decline in the physical function of organism and an increased risk age-related chronic diseases such as cardiovascular diseases, cancer, neurodegenerative diseases. Studies have established that there exist nine hallmarks aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, (ix) altered communication. All these alterations been linked to sustained systemic inflammation, mechanisms contribute timing not clearly determined yet. Nevertheless, dysfunction one most important contributing process. Mitochondria primary endogenous source reactive oxygen species (ROS). During ATP production elevated ROS together with antioxidant defense. Elevated levels can cause oxidative stress severe damage cell, organelle membranes, DNA, lipids, proteins. This contributes phenotype. In this review, we summarize recent advances emphasis on production.

Language: Английский

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Nanomaterials and nanomaterials-based drug delivery to promote cutaneous wound healing

Advanced Drug Delivery Reviews, Journal Year: 2022, Volume and Issue: 193, P. 114670 - 114670

Published: Dec. 17, 2022

Language: Английский

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Aging and chronic inflammation: highlights from a multidisciplinary workshop

Immunity & Ageing, Journal Year: 2023, Volume and Issue: 20(1)

Published: June 8, 2023

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. entails the immune system characterized by decrease thymic output naïve lymphocytes, an accumulated chronic antigenic stress notably caused infections such as cytomegalovirus (CMV), cell senescence with acquisition inflammatory senescence-associated secretory phenotype (SASP). For this reason, due to SASP originating from other tissues, aging commonly accompanied low-grade inflammation, termed "inflammaging". After decades accumulating evidence regarding age-related processes domain now appears mature enough allow integrative reinterpretation old data. Here, we provide overview topics discussed recent workshop "Aging Chronic Inflammation" which many major players field contributed. We highlight advances systematic measurement interpretation biological markers aging, well their implications for human health longevity interventions that can be envisaged maintain or improve function older people.

Language: Английский

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The Skin Microbiome: Current Landscape and Future Opportunities

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3950 - 3950

Published: Feb. 16, 2023

Our skin is the largest organ of body, serving as an important barrier against harsh extrinsic environment. Alongside preventing desiccation, chemical damage and hypothermia, this protects body from invading pathogens through a sophisticated innate immune response co-adapted consortium commensal microorganisms, collectively termed microbiota. These microorganisms inhabit distinct biogeographical regions dictated by physiology. Thus, it follows that perturbations to normal homeostasis, occurs with ageing, diabetes disease, can cause microbial dysbiosis increase infection risk. In review, we discuss emerging concepts in microbiome research, highlighting pertinent links between cutaneous repair. Moreover, address gaps current knowledge highlight key areas requiring further exploration. Future advances field could revolutionise way treat associated ageing other pathologies.

Language: Английский

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Obesity-related kidney disease: Beyond hypertension and insulin-resistance

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 16, 2023

Chronic kidney disease (CKD) causes considerable morbidity, mortality, and health expenditures worldwide. Obesity is a significant risk factor for CKD development, partially explained by the high prevalence of diabetes mellitus hypertension in obese patients. However, adipocytes also possess potent endocrine functions, secreting myriad cytokines adipokines that contribute to insulin resistance induce chronic low-grade inflammatory state thereby damaging kidney. development itself associated with various metabolic alterations exacerbate adipose tissue dysfunction resistance. This adipose-renal axis major focus current research, given rising incidence obesity. Cellular senescence biologic hallmark aging, age another obesity CKD. An elevated senescent cell burden predicts renal animal models, senotherapies may alleviate these phenotypes. In this review, we discuss direct mechanisms which contributes emphasizing potential clinical importance such pathways augmenting care

Language: Английский

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Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 97, P. 102315 - 102315

Published: April 26, 2024

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two types exist where non-small cell lung (NSCLC), accounts for 80–85% and SCLC 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous carcinoma, large carcinoma. Smoking, second-hand smoke, radon gas, asbestos, other pollutants, genetic predisposition, COPD are risk factors. On hand, stresses such DNA damage, telomere shortening, oncogene activation cause a prolonged cycle halt, known senescence. Despite its initial role tumor-suppressing mechanism that slows growth, excessive or improper control this process can age-related diseases, including cancer. Cellular senescence has two purposes in Researchers report tumor growth by constraining multiplication impaired cells. However, senescent cells also demonstrate pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported promote This review will look at cellular cancer, describe diagnostic markers, ask about current treatments it, case studies clinical trials show how senescence-targeting therapies be used talk problems currently being faced, possible solutions same future.

Language: Английский

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Senolytics: from pharmacological inhibitors to immunotherapies, a promising future for patients’ treatment

npj Aging, Journal Year: 2024, Volume and Issue: 10(1)

Published: Feb. 6, 2024

Abstract The involvement of cellular senescence in the initiation and propagation diseases is clearly characterized, making elimination senescent cells essential to treat age-related diseases. development senolytic drugs demonstrated that targeting these limits deterioration patients’ condition, by inducing apoptosis. Nevertheless, first generations senolytics which has been developed displayed their activities through specific mechanisms several limitations during clinical development. However, rational eliminate remains evident, with necessity develop therapies a context tissues. evolutions field drug discovery open way new generation therapies, such as immunological approaches (CAR-T cells, Antibody-Drug Conjugated or vaccines), require preliminary steps research identify markers specifically expressed on demonstrating promising effects. Currently, preclinical strategies appears more challenging avoid strong side effects, but expected results are commensurate hopes for treatments. In this review, we highlight fact classical approach based repurposing display limited efficacy probably reached its term recent complex extension interest domain different fields allow extend possibility discover powerful therapies. future treatment linked cell therapy immunotherapy offer best patients.

Language: Английский

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Macrophage senescence in health and diseases

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(4), P. 1508 - 1524

Published: Jan. 20, 2024

Macrophage senescence, manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype, has long been considered harmful. Persistent senescence macrophages may lead to maladaptation, immune dysfunction, finally development age-related diseases, infections, autoimmune malignancies. However, it is a ubiquitous, multi-factorial, dynamic complex phenomenon that also plays roles in remodeled processes, including wound repair embryogenesis. In this review, we summarize some general molecular changes several specific biomarkers during macrophage which bring new sight recognize senescent different conditions. Also, take an in-depth look at functional macrophages, metabolism, autophagy, polarization, phagocytosis, antigen presentation, infiltration or recruitment. Furthermore, degenerations diseases associated with as well mechanisms relevant genetic regulations are integrated, not only emphasizing possibility regulating benefit age-associated but implication on finding potential targets drugs clinically.

Language: Английский

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Aging, Cellular Senescence, and Glaucoma

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(2), P. 546 - 546

Published: Jan. 1, 2024

Aging is one of the most serious risk factors for glaucoma, and according to age-standardized prevalence, glaucoma second leading cause legal blindness worldwide. Cellular senescence a hallmark aging that defined by stable exit from cell cycle in response cellular damage stress. The potential mechanisms underlying glaucomatous include oxidative stress, DNA damage, mitochondrial dysfunction, defective autophagy/mitophagy, epigenetic modifications. These phenotypes interact generate sufficiently network maintain senescent state. Senescent trabecular meshwork (TM) cells, retinal ganglion cells (RGCs) vascular endothelial reportedly accumulate with age stress may contribute pathologies. Therapies targeting suppression or elimination have been found ameliorate RGC death improve vision models, suggesting pivotal role pathophysiology glaucoma. In this review, we explore biological links between specifically delving into senescence. Moreover, summarize current data on key target associated development clinical Finally, discuss therapeutic management

Language: Английский

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