International Journal of Molecular Sciences

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15 pages, 3490 KiB

Open AccessArticle

Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis

by Hsin-Ying Lu, Chun-Ming Shih, Chun-Yang Huang, Alexander T. H. Wu, Tsai-Mu Cheng, Fwu-Long Mi and Chun-Che Shih

Int. J. Mol. Sci. 2020, 21(21), 8257; https://doi.org/10.3390/ijms21218257 - 4 Nov 2020

Cited by 12 | Viewed by 3695

Abstract

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of [...] Read more.

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1β, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis. Full article

(This article belongs to the Special Issue Inflammaging, Cellular Senescence and Oxidative Stress in Aging and Age-Related Disorders)

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23 pages, 9873 KiB

Open AccessArticle

Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats

by Ali H. El-Far, Mohamed A. Lebda, Ahmed E. Noreldin, Mustafa S. Atta, Yaser H. A. Elewa, Mohamed Elfeky and Shaker A. Mousa

Int. J. Mol. Sci. 2020, 21(12), 4348; https://doi.org/10.3390/ijms21124348 - 18 Jun 2020

Cited by 48 | Viewed by 7281

Abstract

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials [...] Read more.

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1β, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health. Full article

(This article belongs to the Special Issue Inflammaging, Cellular Senescence and Oxidative Stress in Aging and Age-Related Disorders)

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17 pages, 2702 KiB

Open AccessArticle

Loss of C/EBPδ Exacerbates Radiation-Induced Cognitive Decline in Aged Mice due to Impaired Oxidative Stress Response

by Sudip Banerjee, Tyler Alexander, Debajyoti Majumdar, Thomas Groves, Frederico Kiffer, Jing Wang, Akshita Gorantla, Antiño R. Allen and Snehalata A. Pawar

Int. J. Mol. Sci. 2019, 20(4), 885; https://doi.org/10.3390/ijms20040885 - 18 Feb 2019

Cited by 12 | Viewed by 3517

Abstract

Aging is characterized by increased inflammation and deterioration of the cellular stress responses such as the oxidant/antioxidant equilibrium, DNA damage repair fidelity, and telomeric attrition. All these factors contribute to the increased radiation sensitivity in the elderly as shown by epidemiological studies of [...] Read more.

Aging is characterized by increased inflammation and deterioration of the cellular stress responses such as the oxidant/antioxidant equilibrium, DNA damage repair fidelity, and telomeric attrition. All these factors contribute to the increased radiation sensitivity in the elderly as shown by epidemiological studies of the Japanese atomic bomb survivors. There is a global increase in the aging population, who may be at increased risk of exposure to ionizing radiation (IR) as part of cancer therapy or accidental exposure. Therefore, it is critical to delineate the factors that exacerbate age-related radiation sensitivity and neurocognitive decline. The transcription factor CCAAT enhancer binding protein delta (C/EBPδ) is implicated with regulatory roles in neuroinflammation, learning, and memory, however its role in IR-induced neurocognitive decline and aging is not known. The purpose of this study was to delineate the role of C/EBPδ in IR-induced neurocognitive decline in aged mice. We report that aged Cebpd^−/− mice exposed to acute IR exposure display impairment in short-term memory and spatial memory that correlated with significant alterations in the morphology of neurons in the dentate gyrus (DG) and CA1 apical and basal regions. There were no significant changes in the expression of inflammatory markers. However, the expression of superoxide dismutase 2 (SOD2) and catalase (CAT) were altered post-IR in the hippocampus of aged Cebpd^−/− mice. These results suggest that Cebpd may protect from IR-induced neurocognitive dysfunction by suppressing oxidative stress in aged mice. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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26 pages, 2597 KiB

Open AccessArticle

Ginkgolic Acid Rescues Lens Epithelial Cells from Injury Caused by Redox Regulated-Aberrant Sumoylation Signaling by Reviving Prdx6 and Sp1 Expression and Activities

by Bhavana Chhunchha, Prerna Singh, Dhirendra P. Singh and Eri Kubo

Int. J. Mol. Sci. 2018, 19(11), 3520; https://doi.org/10.3390/ijms19113520 - 8 Nov 2018

Cited by 9 | Viewed by 4332

Abstract

Sumoylation is a downstream effector of aging/oxidative stress; excess oxidative stress leads to dysregulation of a specificity protein1 (Sp1) and its target genes, such as Peroxiredoxin 6 (Prdx6), resulting in cellular damage. To cope with oxidative stress, cells rely on a signaling pathway [...] Read more.

Sumoylation is a downstream effector of aging/oxidative stress; excess oxidative stress leads to dysregulation of a specificity protein1 (Sp1) and its target genes, such as Peroxiredoxin 6 (Prdx6), resulting in cellular damage. To cope with oxidative stress, cells rely on a signaling pathway involving redox-sensitive genes. Herein, we examined the therapeutic efficacy of the small molecule Ginkgolic acid (GA), a Sumoylation antagonist, to disrupt aberrant Sumoylation signaling in human and mouse lens epithelial cells (LECs) facing oxidative stress or aberrantly expressing Sumo1 (small ubiquitin-like modifier). We found that GA globally reduced aberrant Sumoylation of proteins. In contrast, Betulinic acid (BA), a Sumoylation agonist, augmented the process. GA increased Sp1 and Prdx6 expression by disrupting the Sumoylation signaling, while BA repressed the expression of both molecules. In vitro DNA binding, transactivation, Sumoylation and expression assays revealed that GA enhanced Sp1 binding to GC-boxes in the Prdx6 promoter and upregulated its transcription. Cell viability and intracellular redox status assays showed that LECs pretreated with GA gained resistance against oxidative stress-driven aberrant Sumoylation signaling. Overall, our study revealed an unprecedented role for GA in LECs and provided new mechanistic insights into the use of GA in rescuing LECs from aging/oxidative stress-evoked dysregulation of Sp1/Prdx6 protective molecules. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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9 pages, 1750 KiB

Open AccessArticle

Tissue-Specific Profiling of Oxidative Stress-Associated Transcriptome in a Healthy Mouse Model

by Jung Min Kim, Hyeong Geug Kim and Chang Gue Son

Int. J. Mol. Sci. 2018, 19(10), 3174; https://doi.org/10.3390/ijms19103174 - 15 Oct 2018

Cited by 35 | Viewed by 5681

Abstract

Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes including aging. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability especially to age-related and chronic diseases. In [...] Read more.

Oxidative stress is a common phenomenon and is linked to a wide range of diseases and pathological processes including aging. Tissue-specific variation in redox signaling and cellular responses to oxidative stress may be associated with vulnerability especially to age-related and chronic diseases. In order to provide a basis for tissue-specific difference, we examined the tissue-specific transcriptional features of 101 oxidative stress-associated genes in 10 different tissues and organs of healthy mice under physiological conditions. Microarray analysis results, which were consistent with quantitative polymerase chain reaction (qPCR) results, showed that catalase, Gpx3, and Gpx4 were most highly regulated in the liver, kidney, and testes. We also found the tissue-specific gene expression of SOD1 (liver and kidney), SOD2 (heart and muscle), and SOD3 (lung and kidney). The current results will serve as a reference for animal models and help advance our understanding of tissue-specific variability in oxidative stress-associated pathogenesis. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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19 pages, 2575 KiB

Open AccessArticle

Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9 Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation

by Yi-Heng Lee, Hao-Chieh Hsu, Pei-Chen Kao, Young-Ji Shiao, Skye Hsin-Hsien Yeh, Feng-Shiun Shie, Shu-Meng Hsu, Chih-Wen Yeh, Hui-Kang Liu, Shi-Bing Yang and Huey-Jen Tsay

Int. J. Mol. Sci. 2018, 19(8), 2333; https://doi.org/10.3390/ijms19082333 - 8 Aug 2018

Cited by 30 | Viewed by 7433

Abstract

Alzheimer’s disease (AD), a progressive neurodegenerative disease is highly associated with metabolic syndromes. We previously demonstrated that glycemic dysregulation and obesity are augmented in high fat diet (HFD)-treated APPswe/PS1dE9 (APP/PS1) transgenic mice. In the current study, the underlying mechanism mediating exacerbated metabolic stresses [...] Read more.

Alzheimer’s disease (AD), a progressive neurodegenerative disease is highly associated with metabolic syndromes. We previously demonstrated that glycemic dysregulation and obesity are augmented in high fat diet (HFD)-treated APPswe/PS1dE9 (APP/PS1) transgenic mice. In the current study, the underlying mechanism mediating exacerbated metabolic stresses in HFD APP/PS1 transgenic mice was further examined. APP/PS1 mice developed insulin resistance and, consequently, impaired glucose homeostasis after 10 weeks on HFD. [¹⁸F]-2-fluoro-2-deoxy-d-glucose ([¹⁸F]-FDG) positron emission tomography showed that interscapular brown adipose tissue is vulnerable to HFD and AD-related pathology. Chronic HFD induced hyperphagia, with limited effects on basal metabolic rates in APP/PS1 transgenic mice. Excessive food intake may be caused by impairment of leptin signaling in the hypothalamus because leptin failed to suppress the food intake of HFD APP/PS1 transgenic mice. Leptin-induced pSTAT3 signaling in the arcuate nucleus was attenuated. Dysregulated energy homeostasis including hyperphagia and exacerbated obesity was elicited prior to the presence of the amyloid pathology in the hypothalamus of HFD APP/PS1 transgenic mice; nevertheless, cortical neuroinflammation and the level of serum Aβ and IL-6 were significantly elevated. Our study demonstrates the pivotal role of AD-related pathology in augmenting HFD-induced insulin and leptin resistance and impairing hypothalamic regulation of energy homeostasis. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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14 pages, 2543 KiB

Open AccessArticle

Impact of Long-Term RF-EMF on Oxidative Stress and Neuroinflammation in Aging Brains of C57BL/6 Mice

by Ye Ji Jeong, Yeonghoon Son, Na-Kyung Han, Hyung-Do Choi, Jeong-Ki Pack, Nam Kim, Yun-Sil Lee and Hae-June Lee

Int. J. Mol. Sci. 2018, 19(7), 2103; https://doi.org/10.3390/ijms19072103 - 19 Jul 2018

Cited by 33 | Viewed by 6685

Abstract

The expansion of mobile phone use has raised questions regarding the possible biological effects of radiofrequency electromagnetic field (RF-EMF) exposure on oxidative stress and brain inflammation. Despite accumulative exposure of humans to radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, their long-term effects on [...] Read more.

The expansion of mobile phone use has raised questions regarding the possible biological effects of radiofrequency electromagnetic field (RF-EMF) exposure on oxidative stress and brain inflammation. Despite accumulative exposure of humans to radiofrequency electromagnetic fields (RF-EMFs) from mobile phones, their long-term effects on oxidative stress and neuroinflammation in the aging brain have not been studied. In the present study, middle-aged C57BL/6 mice (aged 14 months) were exposed to 1950 MHz electromagnetic fields for 8 months (specific absorption rate (SAR) 5 W/kg, 2 h/day, 5 d/week). Compared with those in the young group, levels of protein (3-nitro-tyrosine) and lipid (4-hydroxy-2-nonenal) oxidative damage markers were significantly increased in the brains of aged mice. In addition, levels of markers for DNA damage (8-hydroxy-2′-deoxyguanosine, p53, p21, γH2AX, and Bax), apoptosis (cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase 1 (PARP-1)), astrocyte (GFAP), and microglia (Iba-1) were significantly elevated in the brains of aged mice. However, long-term RF-EMF exposure did not change the levels of oxidative stress, DNA damage, apoptosis, astrocyte, or microglia markers in the aged mouse brains. Moreover, long-term RF-EMF exposure did not alter locomotor activity in aged mice. Therefore, these findings indicate that long-term exposure to RF-EMF did not influence age-induced oxidative stress or neuroinflammation in C57BL/6 mice. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Open AccessArticle

The Contribution of Oxidative Stress and Inflamm-Aging in Human and Equine Asthma

by Michela Bullone and Jean-Pierre Lavoie

Int. J. Mol. Sci. 2017, 18(12), 2612; https://doi.org/10.3390/ijms18122612 - 5 Dec 2017

Cited by 57 | Viewed by 11879

Abstract

Aging is associated with a dysregulation of the immune system, leading to a general pro-inflammatory state of the organism, a process that has been named inflamm-aging. Oxidative stress has an important role in aging and in the regulation of immune responses, probably playing [...] Read more.

Aging is associated with a dysregulation of the immune system, leading to a general pro-inflammatory state of the organism, a process that has been named inflamm-aging. Oxidative stress has an important role in aging and in the regulation of immune responses, probably playing a role in the development of age-related diseases. The respiratory system function physiologically declines with the advancement of age. In elderly asthmatic patients, this may contribute to disease expression. In this review, we will focus on age-related changes affecting the immune system and in respiratory structure and function that could contribute to asthma occurrence, and/or clinical presentation in the elderly. Also, naturally occurring equine asthma will be discussed as a possible model for studying the importance of oxidative stress and immun-aging/inflamm-aging in humans. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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7598 KiB

Open AccessArticle

Differential Expression of Nitric Oxide Synthase Isoforms nNOS and iNOS in Patients with Non-Segmental Generalized Vitiligo

by Mario Vaccaro, Natasha Irrera, Giuseppina Cutroneo, Giuseppina Rizzo, Federico Vaccaro, Giuseppe P. Anastasi, Francesco Borgia, Serafinella P. Cannavò, Domenica Altavilla and Francesco Squadrito

Int. J. Mol. Sci. 2017, 18(12), 2533; https://doi.org/10.3390/ijms18122533 - 26 Nov 2017

Cited by 27 | Viewed by 5914

Abstract

Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis is still not well understood. Exposure to UVA and UVB induces nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, increasing tyrosinase [...] Read more.

Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis is still not well understood. Exposure to UVA and UVB induces nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, increasing tyrosinase activity and melanin synthesis, whereas inducible nitric oxide synthase over expression might be involved in hypopigmentary disorders. The aim of this study was to evaluate whether inducible nitric oxide synthase and neuronal nitric oxide synthase expression were modified in vitiligo skin compared to healthy controls. Skin biopsies were obtained from inflammatory/lesional and white/lesional skin in 12 patients with active, non-segmental vitiligo; site-matched biopsies of normal skin from eight patients were used as controls. Nitric oxide synthase isoforms expression was evaluated by confocal laser scanning microscopy and Western Blot analysis. Inducible nitric oxide synthase expression was significantly increased in inflammatory/lesional skin compared to healthy skin; melanocytes showed a moderate neuronal nitric oxide synthase expression in white/lesional skin, demonstrating that metabolic function still goes on. The obtained data demonstrated that vitiligo lesions were characterized by modifications of nitric oxide synthase isoforms, thus confirming the hypothesis that nitric oxide imbalance is involved in vitiligo and supporting the idea that nitric oxide synthase inhibitors might be used as a possible therapeutic approach for the management of vitiligo. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Open AccessArticle

Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

by Beatrice Menicacci, Caterina Cipriani, Francesca Margheri, Alessandra Mocali and Lisa Giovannelli

Int. J. Mol. Sci. 2017, 18(11), 2275; https://doi.org/10.3390/ijms18112275 - 30 Oct 2017

Cited by 48 | Viewed by 7844

Abstract

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have [...] Read more.

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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3007 KiB

Open AccessArticle

Antioxidant Defence, Oxidative Stress and Oxidative Damage in Saliva, Plasma and Erythrocytes of Dementia Patients. Can Salivary AGE be a Marker of Dementia?

by Magdalena Choromańska, Anna Klimiuk, Paula Kostecka-Sochoń, Karolina Wilczyńska, Mikołaj Kwiatkowski, Natalia Okuniewska, Napoleon Waszkiewicz, Anna Zalewska and Mateusz Maciejczyk

Int. J. Mol. Sci. 2017, 18(10), 2205; https://doi.org/10.3390/ijms18102205 - 20 Oct 2017

Cited by 71 | Viewed by 7000

Abstract

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide [...] Read more.

Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2’-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Review

Jump to: Research

39 pages, 2272 KiB

Open AccessReview

Inflammaging and Oxidative Stress in Human Diseases: From Molecular Mechanisms to Novel Treatments

by Li Zuo, Evan R. Prather, Mykola Stetskiv, Davis E. Garrison, James R. Meade, Timotheus I. Peace and Tingyang Zhou

Int. J. Mol. Sci. 2019, 20(18), 4472; https://doi.org/10.3390/ijms20184472 - 10 Sep 2019

Cited by 324 | Viewed by 19730

Abstract

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead [...] Read more.

It has been proposed that a chronic state of inflammation correlated with aging known as inflammaging, is implicated in multiple disease states commonly observed in the elderly population. Inflammaging is associated with over-abundance of reactive oxygen species in the cell, which can lead to oxidation and damage of cellular components, increased inflammation, and activation of cell death pathways. This review focuses on inflammaging and its contribution to various age-related diseases such as cardiovascular disease, cancer, neurodegenerative diseases, chronic obstructive pulmonary disease, diabetes, and rheumatoid arthritis. Recently published mechanistic details of the roles of reactive oxygen species in inflammaging and various diseases will also be discussed. Advancements in potential treatments to ameliorate inflammaging, oxidative stress, and consequently, reduce the morbidity of multiple disease states will be explored. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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20 pages, 3012 KiB

Open AccessReview

The Link Between Inflammaging and Degenerative Joint Diseases

by Elena Rezuș, Anca Cardoneanu, Alexandra Burlui, Andrei Luca, Cătălin Codreanu, Bogdan Ionel Tamba, Gabriela-Dumitrița Stanciu, Nicoleta Dima, Codruța Bădescu and Ciprian Rezuș

Int. J. Mol. Sci. 2019, 20(3), 614; https://doi.org/10.3390/ijms20030614 - 31 Jan 2019

Cited by 68 | Viewed by 11081

Abstract

Aging is an inevitable process in the human body that is associated with a multitude of systemic and localized changes. All these conditions have a common pathogenic mechanism characterized by the presence of a low-grade proinflammatory status. Inflammaging refers to all the processes [...] Read more.

Aging is an inevitable process in the human body that is associated with a multitude of systemic and localized changes. All these conditions have a common pathogenic mechanism characterized by the presence of a low-grade proinflammatory status. Inflammaging refers to all the processes that contribute to the occurrence of various diseases associated with aging such as frailty, atherosclerosis, Alzheimer’s disease, sarcopenia, type 2 diabetes, or osteoarthritis. Inflammaging is systemic, chronic, and asymptomatic. Osteoarthritis and many age-related degenerative joint diseases are correlated with aging mechanisms such as the presence of an inflammatory microenvironment and the impaired link between inflammasomes and autophagy. There is a close relationship between chondrocyte activity and local articular environment changes due to cell senescence, followed by secretion of inflammatory mediators. In addition, systemic inflammaging can lead to cartilage destruction, pain, disability, and an impaired quality of life. The purpose of this review is to summarize the main mechanisms implicated in inflammaging and the connection it has with degenerative joint diseases. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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30 pages, 350 KiB

Open AccessReview

Reactive Oxygen Species-Mediated Damage of Retinal Neurons: Drug Development Targets for Therapies of Chronic Neurodegeneration of the Retina

by Landon J. Rohowetz, Jacob G. Kraus and Peter Koulen

Int. J. Mol. Sci. 2018, 19(11), 3362; https://doi.org/10.3390/ijms19113362 - 27 Oct 2018

Cited by 67 | Viewed by 6201

Abstract

The significance of oxidative stress in the development of chronic neurodegenerative diseases of the retina has become increasingly apparent in recent years. Reactive oxygen species (ROS) are free radicals produced at low levels as a result of normal cellular metabolism that are ultimately [...] Read more.

The significance of oxidative stress in the development of chronic neurodegenerative diseases of the retina has become increasingly apparent in recent years. Reactive oxygen species (ROS) are free radicals produced at low levels as a result of normal cellular metabolism that are ultimately metabolized and detoxified by endogenous and exogenous mechanisms. In the presence of oxidative cellular stress, ROS are produced in excess, resulting in cellular injury and death and ultimately leading to tissue and organ dysfunction. Recent studies have investigated the role of excess ROS in the pathogenesis and development of chronic neurodegenerative diseases of the retina including glaucoma, diabetic retinopathy, and age-related macular degeneration. Findings from these studies are promising insofar as they provide clear rationales for innovative treatment and prevention strategies of these prevalent and disabling diseases where currently therapeutic options are limited. Here, we briefly outline recent developments that have contributed to our understanding of the role of ROS in the pathogenesis of chronic neurodegenerative diseases of the retina. We then examine and analyze the peer-reviewed evidence in support of ROS as targets for therapy development in the area of chronic neurodegeneration of the retina. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Open AccessReview

Of Energy and Entropy: The Ineluctable Impact of Aging in Old Age Dementia

by Virginia Boccardi, Chiara Comanducci, Marta Baroni and Patrizia Mecocci

Int. J. Mol. Sci. 2017, 18(12), 2672; https://doi.org/10.3390/ijms18122672 - 9 Dec 2017

Cited by 29 | Viewed by 5511

Abstract

Alzheimer’s disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to [...] Read more.

Alzheimer’s disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to genetic mutations, late-onset AD is more likely due to a gradual accumulation of age-related modifications. “Normal brain aging” and AD may represent different pathways of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes (ARCs) affecting the brain may be considered as biologic manifestations of increasing entropy, a measure of disorder. Late-onset AD may be regarded as the final effect of a reduced energy production, due to exhausted mitochondria, and an increased entropy in the brain. This unique trajectory enables a bioenergetics-centered strategy targeting disease-stage specific profile of brain metabolism for disease prevention and treatment. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Open AccessReview

by Anna A. Boyko, Natalya I. Troyanova, Elena I. Kovalenko and Alexander M. Sapozhnikov

Int. J. Mol. Sci. 2017, 18(12), 2633; https://doi.org/10.3390/ijms18122633 - 6 Dec 2017

Cited by 39 | Viewed by 8406

Abstract

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common age-related neurodegenerative disorders. Both diseases are characterized by chronic inflammation in the brain—neuroinflammation. The first signs of PD and AD are most often manifested in old age, in which the immune system [...] Read more.

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are the most common age-related neurodegenerative disorders. Both diseases are characterized by chronic inflammation in the brain—neuroinflammation. The first signs of PD and AD are most often manifested in old age, in which the immune system is usually characterized by chronic inflammation, so-called “inflammaging” In recent years, there is growing evidence that pathogenesis of these diseases is connected with both regional and peripheral immune processes. Currently, the association of clinical signs of PD and AD with different characteristics of patient immune status is actively being researched. In this mini-review we compare the association of PD and AD alterations of a number of immune system parameters connected with the process of inflammation. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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Open AccessReview

Nitroxides as Antioxidants and Anticancer Drugs

by Marcin Lewandowski and Krzysztof Gwozdzinski

Int. J. Mol. Sci. 2017, 18(11), 2490; https://doi.org/10.3390/ijms18112490 - 22 Nov 2017

Cited by 91 | Viewed by 9861

Abstract

Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic [...] Read more.

Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic nitroxide derivatives of piperidine, pyrroline and pyrrolidine. The antioxidant action of nitroxides is associated with their redox cycle. Nitroxides, unlike other antioxidants, are characterized by a catalytic mechanism of action associated with a single electron oxidation and reduction reaction. In biological conditions, they mimic superoxide dismutase (SOD), modulate hemoprotein’s catalase-like activity, scavenge reactive free radicals, inhibit the Fenton and Haber-Weiss reactions and suppress the oxidation of biological materials (peptides, proteins, lipids, etc.). The use of nitroxides as antioxidants against oxidative stress induced by anticancer drugs has also been investigated. The application of nitroxides and their derivatives as anticancer drugs is discussed in the contexts of breast, hepatic, lung, ovarian, lymphatic and thyroid cancers under in vivo and in vitro experiments. In this article, we focus on new natural spin-labelled derivatives such as camptothecin, rotenone, combretastatin, podophyllotoxin and others. The applications of nitroxides in the aging process, cardiovascular disease and pathological conditions were also discussed. Full article

(This article belongs to the Special Issue Inflammaging and Oxidative Stress in Aging and Age-Related Disorders)

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