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Antioxidants
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Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related...
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Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 25319

Special Issue Editor

Dr. Morana Jaganjac

E-Mail Website
Guest Editor
Laboratory for Oxidative Stress (LabOS), Division of Molecular Medicine, Ruder Boskovic Institute, HR-10000 Zagreb, Croatia
Interests: oxidative stress; lipid peroxidation; redox proteomics; metabolic profiling; toxicology; inflammation; metabolic syndrome; carcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS) were first perceived as toxic by-products of normal metabolism. Today, ROS are known to also serve as important signaling molecules that modulate different physiological and pathological processes. The type of ROS generated, its reactivity, diffusion distance, and the vicinity of the molecular target determine whether the signal will be translated further. ROS serve as both intracellular and intercellular messengers and may thus also orchestrate the fate of the surrounding cells. A shift in the equilibrium within the redox system can either promote cellular adaptation or impair the physiology of the cell. Throughout an individual’s lifetime, ROS-induced cellular damage accumulates and contributes to the aging process and the development of age-related diseases. Among the oxidative stress-induced age-related diseases are cardiovascular disorders, neurodegenerative disorders, metabolic syndrome, and cancer. This Special Issue aims to bring together original research and review articles related to the role of ROS as cellular messengers in both the physiology and pathophysiology of aging.

We look forward to your contribution.

Dr. Morana Jaganjac
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Reactive oxygen species
  • Aging
  • Age-related diseases

Published Papers (7 papers)

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Research

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17 pages, 3568 KiB  
Article
Mechanism of Action of Cyanidin 3-O-Glucoside in Gluconeogenesis and Oxidative Stress-Induced Cancer Cell Senescence
by Yaoyao Jia, Chunyan Wu, Adriana Rivera-Piza, Yeon-Ji Kim, Ji Hae Lee and Sung-Joon Lee
Antioxidants 2022, 11(4), 749; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11040749 - 09 Apr 2022
Cited by 9 | Viewed by 2553
Abstract
Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular [...] Read more.
Cyanidin-3-O-glucoside (C3G) is a natural anthocyanin abundant in fruits and vegetables that interacts and possibly modulates energy metabolism and oxidative stress. This study investigated the effect of C3G on gluconeogenesis and cancer cell senescence. C3G activates adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor involved in metabolism and the aging process. C3G suppressed hepatic gluconeogenesis by reducing the expression of gluconeogenic genes through the phosphorylation inactivation of CRTC2 and HDAC5 coactivators via AMPK. C3G did not directly interact with AMPK but, instead, activated AMPK through the adiponectin receptor signaling pathway, as demonstrated through adiponectin receptor gene knockdown experiments. In addition, C3G increased cellular AMP levels in cultured hepatocytes, and the oral administration of C3G in mice elevated their plasma adiponectin concentrations. These effects collectively contribute to the activation of AMPK. In addition, C3G showed potent antioxidant activity and induced cellular senescence, and apoptosis in oxidative-stress induced senescence in hepatocarcinoma cells. C3G increased senescence-associated β-galactosidase expression, while increasing the expression levels of P16, P21 and P53, key markers of cellular senescence. These findings demonstrate that anthocyanin C3G achieves hypoglycemic effects via AMPK activation and the subsequent suppression of gluconeogenesis and exhibits anti-cancer activity through the induction of apoptosis and cellular senescence. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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14 pages, 2049 KiB  
Article
Deuterated Arachidonic Acid Ameliorates Lipopolysaccharide-Induced Lung Damage in Mice
by Alla Y. Molchanova, Svetlana N. Rjabceva, Tigran B. Melik-Kasumov, Nikolay B. Pestov, Plamena R. Angelova, Vadim V. Shmanai, Olga L. Sharko, Andrei V. Bekish, Genevieve James, Hui Gyu Park, Irina A. Udalova, J. Thomas Brenna and Mikhail S. Shchepinov
Antioxidants 2022, 11(4), 681; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11040681 - 31 Mar 2022
Cited by 5 | Viewed by 2396
Abstract
Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at [...] Read more.
Arachidonic acid (ARA) is a major component of lipid bilayers as well as the key substrate for the eicosanoid cascades. ARA is readily oxidized, and its non-enzymatic and enzymatic oxidation products induce inflammatory responses in nearly all tissues, including lung tissues. Deuteration at bis-allylic positions substantially decreases the overall rate of ARA oxidation when hydrogen abstraction is an initiating event. To compare the effects of dosing of arachidonic acid (H-ARA) and its bis-allylic hexadeuterated form (D-ARA) on lungs in conventionally healthy mice and in an acute lung injury model, mice were dosed with H-ARA or D-ARA for six weeks through dietary supplementation and then challenged with intranasal lipopolysaccharide (LPS) for subsequent analysis of bronchoalveolar lavage fluid and lung tissue. Dosing on D-ARA resulted in successful incorporation of D-ARA into various tissues. D-ARA significantly reduced LPS-induced adverse effects on alveolar septal thickness and the bronchoalveolar area. Oral deuterated ARA is taken up efficiently and protects against adverse LPS-induced pathology. This suggests novel therapeutic avenues for reducing lung damage during severe infections and other pathological conditions with inflammation in the pulmonary system and other inflammatory diseases. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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13 pages, 2575 KiB  
Article
Key Mechanisms and Potential Implications of Hericium erinaceus in NLRP3 Inflammasome Activation by Reactive Oxygen Species during Alzheimer’s Disease
by Marika Cordaro, Angela Trovato Salinaro, Rosalba Siracusa, Ramona D’Amico, Daniela Impellizzeri, Maria Scuto, Maria Laura Ontario, Salvatore Cuzzocrea, Rosanna Di Paola, Roberta Fusco and Vittorio Calabrese
Antioxidants 2021, 10(11), 1664; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111664 - 22 Oct 2021
Cited by 29 | Viewed by 4534
Abstract
Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional [...] Read more.
Alzheimer’s disease (AD) is the principal cause of dementia, and its incidence increases with age. Altered antioxidant systems and inflammation have an important role in the etiology of neurodegenerative disorders. In this study, we evaluated the effects of Hericium erinaceus, a nutritional mushroom with important antioxidant effects, in a rat model of AD. Animals were injected with 70 mg/Kg of AlCl3 daily for 6 weeks, and Hericium erinaceus was administered daily by gavage. Before the experiment’s end date, behavioral test training was performed. At the end of the study, behavioral changes were assessed, and the animals were euthanized. Brain tissues were harvested for further analysis. AlCl3 mainly accumulates in the hippocampus, the principal region of the brain involved in memory functions and learning. Hericium erinaceus administration reduced behavioral changes and hippocampal neuronal degeneration. Additionally, it reduced phosphorylated Tau levels, aberrant APP overexpression, and β-amyloid accumulation. Moreover, Hericium erinaceus decreased the pro-oxidative and pro-inflammatory hippocampal alterations induced by AD. In particular, it reduced the activation of the NLRP3 inflammasome components, usually activated by increased oxidative stress during AD. Collectively, our results showed that Hericium erinaceus has protective effects on behavioral alteration and histological modification associated with AD due to the modulation of the oxidative and inflammatory pathways, as well as regulating cellular brain stress. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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16 pages, 2249 KiB  
Article
Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes
by Maha Sellami, Shamma Al-muraikhy, Hend Al-Jaber, Hadaia Al-Amri, Layla Al-Mansoori, Nayef A. Mazloum, Francesco Donati, Francesco Botre and Mohamed A. Elrayess
Antioxidants 2021, 10(7), 1035; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071035 - 28 Jun 2021
Cited by 23 | Viewed by 4592
Abstract
Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. In this study, 80 blood samples [...] Read more.
Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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25 pages, 5222 KiB  
Article
Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes
by Aisha Y. Madani, Yasser Majeed, Houari B. Abdesselem, Maha V. Agha, Muneera Vakayil, Nour K. Al Sukhun, Najeeb M. Halabi, Pankaj Kumar, Shahina Hayat, Mohamed A. Elrayess, Arash Rafii, Karsten Suhre and Nayef A. Mazloum
Antioxidants 2021, 10(2), 334; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10020334 - 23 Feb 2021
Cited by 12 | Viewed by 4769
Abstract
Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that [...] Read more.
Obesity promotes premature aging and dysfunction of white adipose tissue (WAT) through the accumulation of cellular senescence. The senescent cells burden in WAT has been linked to inflammation, insulin-resistance (IR), and type 2 diabetes (T2D). There is limited knowledge about molecular mechanisms that sustain inflammation in obese states. Here, we describe a robust and physiologically relevant in vitro system to trigger senescence in mouse 3T3-L1 preadipocytes. By employing transcriptomics analyses, we discovered up-regulation of key pro-inflammatory molecules and activation of interferon/signal transducer and activator of transcription (STAT)1/3 signaling in senescent preadipocytes, and expression of downstream targets was induced in epididymal WAT of obese mice, and obese human adipose tissue. To test the relevance of STAT1/3 signaling to preadipocyte senescence, we used Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology to delete STAT1/3 and discovered that STAT1 promoted growth arrest and cooperated with cyclic Guanosine Monophosphate-Adenosine Monophosphate (GMP-AMP) synthase-stimulator of interferon genes (cGAS-STING) to drive the expression of interferon β (IFNβ), C-X-C motif chemokine ligand 10 (CXCL10), and interferon signaling-related genes. In contrast, we discovered that STAT3 was a negative regulator of STAT1/cGAS-STING signaling—it suppressed senescence and inflammation. These data provide insights into how STAT1/STAT3 signaling coordinates senescence and inflammation through functional interactions with the cGAS/STING pathway. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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Review

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14 pages, 972 KiB  
Review
Lipid Peroxidation in Obesity: Can Bariatric Surgery Help?
by Ana Maria Soldo, Ivo Soldo, Andrija Karačić, Marcela Konjevod, Matea Nikolac Perkovic, Tanja Matijevic Glavan, Martina Luksic, Neven Žarković and Morana Jaganjac
Antioxidants 2022, 11(8), 1537; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081537 - 07 Aug 2022
Cited by 5 | Viewed by 2368
Abstract
Obesity and chronic oxidative stress, often being associated with each other in a vicious circle, are important factors of chronic diseases. Although it was usually considered to accompany aging and wealth, global trends show the increase in obesity among children even in Third [...] Read more.
Obesity and chronic oxidative stress, often being associated with each other in a vicious circle, are important factors of chronic diseases. Although it was usually considered to accompany aging and wealth, global trends show the increase in obesity among children even in Third World countries. Being manifested by an imbalance between energy consumption and food intake, obesity is characterized by an excessive or abnormal fat accumulation, impaired redox homeostasis and metabolic changes often associated with the self-catalyzed lipid peroxidation generating 4-hydroxynonenal, pluripotent bioactive peroxidation product of polyunsaturated fatty acids. Conservative methods targeting obesity produced only modest and transient results in the treatment of morbid obesity. Therefore, in recent years, surgery, primarily bariatric, became an attractive treatment for morbid obesity. Since adipose tissue is well known as a stress organ with pronounced endocrine functions, surgery results in redox balance and metabolic improvement of the entire organism. The source of bioactive lipids and lipid-soluble antioxidants, and the complex pathophysiology of lipid peroxidation should thus be considered from the aspects of personalized and integrative biomedicine to treat obesity in an appropriate way. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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13 pages, 664 KiB  
Review
Oxidative Stress Parameters as Biomarkers of Cardiovascular Disease towards the Development and Progression
by Amanda Shen-Yee Kong, Kok Song Lai, Cheng-Wan Hee, Jiun Yan Loh, Swee Hua Erin Lim and Maran Sathiya
Antioxidants 2022, 11(6), 1175; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061175 - 15 Jun 2022
Cited by 13 | Viewed by 3119
Abstract
Cardiovascular disease (CVD) remains the leading cause of death globally, with unhealthy lifestyles today greatly increasing the risk. Over the decades, scientific investigation has been carried out on reactive oxygen species (ROS) and their resultant oxidative stress based on their changes made on [...] Read more.
Cardiovascular disease (CVD) remains the leading cause of death globally, with unhealthy lifestyles today greatly increasing the risk. Over the decades, scientific investigation has been carried out on reactive oxygen species (ROS) and their resultant oxidative stress based on their changes made on biological targets such as lipids, proteins, and DNA. Since the existing clinical studies with antioxidants failed to provide relevant findings on CVD prediction, the focus has shifted towards recognition of oxidised targets as biomarkers to predict prognosis and response to accurate treatment. The identification of redox markers could help clinicians in providing risk stratification for CVD events beyond the traditional prognostic and diagnostic targets. This review will focus on how oxidant-related parameters can be applied as biomarkers for CVD based on recent clinical evidence. Full article
(This article belongs to the Special Issue Reactive Oxygen Species as Cellular Messengers in Aging and Age-Related Diseases)
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