Development of age-dependent glomerular lesions in galectin-3/AGE-receptor-3 knockout mice

2005 ◽  
Vol 289 (3) ◽  
pp. F611-F621 ◽  
Author(s):  
Carla Iacobini ◽  
Giovanna Oddi ◽  
Stefano Menini ◽  
Lorena Amadio ◽  
Carlo Ricci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Disease ◽  
Structural Parameters ◽  
Glomerular Sclerosis ◽  
Low Grade ◽  
Age Related ◽  
Age Dependent ◽  
Glomerular Lesions ◽  
Galectin 3

Aging is characterized by renal functional and structural abnormalities resembling those observed in diabetes. These changes have been related to the progressive accumulation of advanced glycation end-products (AGEs) and cumulative oxidative stress occurring in both conditions. We previously reported that galectin-3 ablation is associated with increased susceptibility to diabetes- and AGE-induced glomerulopathy, thus indicating a protective role of galectin-3 as an AGE receptor. To investigate the role of the AGE/AGE receptor pathway in the pathogenesis of age-related renal disease, we evaluated the development of glomerular lesions in aging galectin-3 knockout (KO) vs. wild-type (WT) mice and their relation to the increased AGE levels and oxidative stress characterizing the aging process. KO mice showed significantly more pronounced age-dependent increases in proteinuria, albuminuria, glomerular sclerosis, and glomerular and mesangial areas, starting at 18 mo, as well as renal extracellular matrix mRNA and protein expression, starting at 12 mo vs. age-matched WT mice. Circulating and renal AGEs, plasma isoprostane 8-epi-PGF2α levels, glomerular content of the glycoxidation and lipoxidation products Nε-carboxymethyllysine and 4-hydroxy-2-nonenal, and renal nuclear factor-κB activity also increased more markedly with age in KO than WT mice. AGE levels correlated significantly with renal functional and structural parameters. These data indicate that aging galectin-3 KO mice develop more pronounced changes in renal function and structure than coeval WT mice, in parallel with a more marked degree of AGE accumulation, oxidative stress, and associated low-grade inflammation, thus supporting the concept that the AGE/AGE receptor pathway is implicated in age-related renal disease.

scholarly journals Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

2016 ◽  
Author(s):  
Tania Rescigno ◽  
Mario F. Tecce ◽  
Anna Capasso
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Aging Process ◽  
Bioactive Molecules ◽  
Low Grade ◽  
Molecular Processes ◽  
Ample Evidence ◽  
Inflammatory Status ◽  
Age Related

The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.

scholarly journals The Role of Oxidative Stress and Inflammation in Cardiovascular Aging

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Junzhen Wu ◽  
Shijin Xia ◽  
Bill Kalionis ◽  
Wenbin Wan ◽  
Tao Sun
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Ventricular Hypertrophy ◽  
Left Ventricular ◽  
Low Grade ◽  
Oxygen Species ◽  
Age Related ◽  
Vascular Elasticity ◽  
Low Grade Inflammation

Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.

The role of p66Shc deletion in age-associated arterial dysfunction and disease states

2008 ◽  
Vol 105 (5) ◽  
pp. 1628-1631 ◽  
Author(s):  
Giovanni G. Camici ◽  
Francesco Cosentino ◽  
Felix C. Tanner ◽  
Thomas F. Lüscher
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Adaptor Protein ◽  
Oxygen Species ◽  
Potential Implication ◽  
Disease States ◽  
Age Related ◽  
Related Risk ◽  
Age Dependent

Accumulation of oxidative stress with age is hypothesized to be the primary causative mediator of age-associated diseases. Among different tissues, aging vessels are known to accumulate oxidative damage and undergo functional impairment. Oxidative stress affects the availability and/or balance of key regulators of vascular homeostasis and favors the development of cardiovascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in the cytoplasm and in the mitochondria. The mitochondrial enzyme p66Shc is an adaptor protein and plays an important role as a redox enzyme implicated in mitochondrial eactive oxygen species generation and translation of oxidative signals into apoptosis. Mice lacking p66Shc−/− gene display reduced production of intracellular oxidants and a 30% prolonged life span. For this reasons, a series of studies conceived to elucidate the function of p66Shc and its possible implication in age-associated cardiovascular diseases have been carried out. Indeed, p66Shc−/− mice have been shown to be protected from age-dependent endothelial dysfunction as well as age-related risk factors such as diabetes and hypercholesterolemia. This review focuses on delineating the role of the p66Shc adaptor protein and its potential implication in the pathophysiology of aging and age-related cardiovascular disease.

scholarly journals Oxidative damage to DNA and antioxidant status in aging and age-related diseases.

2007 ◽  
Vol 54 (1) ◽  
pp. 11-26 ◽  
Author(s):  
Ryszard Olinski ◽  
Agnieszka Siomek ◽  
Rafal Rozalski ◽  
Daniel Gackowski ◽  
Marek Foksinski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Single Cells ◽  
Cellular Level ◽  
Pathological Conditions ◽  
Age Related ◽  
Complex Process ◽  
Age Dependent ◽  
Oxidatively Modified ◽  
Oxidative Damage To Dna

Aging is a complex process involving morphologic and biochemical changes in single cells and in the whole organism. One of the most popular explanations of how aging occurs at the molecular level is the oxidative stress hypothesis. Oxidative stress leads in many cases to an age-dependent increase in the cellular level of oxidatively modified macromolecules including DNA, and it is this increase which has been linked to various pathological conditions, such as aging, carcinogenesis, neurodegenerative and cardiovascular diseases. It is, however, possible that a number of short-comings associated with gaps in our knowledge may be responsible for the failure to produce definite results when applied to understanding the role of DNA damage in aging and age-related diseases.

scholarly journals The Role of Immune Cells in Oxi-Inflamm-Aging

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2974
Author(s):  
Irene Martínez de Toda ◽  
Noemi Ceprián ◽  
Estefanía Diaz-Del Cerro ◽  
Mónica De la Fuente
Keyword(s):  
Oxidative Stress ◽  
Immune System ◽  
Immune Cells ◽  
Low Grade ◽  
Inflammatory Stress ◽  
Immune Systems ◽  
Age Related ◽  
Chronic Oxidative Stress ◽  
Inflammatory State

Aging is the result of the deterioration of the homeostatic systems (nervous, endocrine, and immune systems), which preserve the organism’s health. We propose that the age-related impairment of these systems is due to the establishment of a chronic oxidative stress situation that leads to low-grade chronic inflammation throughout the immune system’s activity. It is known that the immune system weakens with age, which increases morbidity and mortality. In this context, we describe how the function of immune cells can be used as an indicator of the rate of aging of an individual. In addition to this passive role as a marker, we describe how the immune system can work as a driver of aging by amplifying the oxidative-inflammatory stress associated with aging (oxi-inflamm-aging) and inducing senescence in far tissue cells. Further supporting our theory, we discuss how certain lifestyle conditions (such as social environment, nutrition, or exercise) can have an impact on longevity by affecting the oxidative and inflammatory state of immune cells, regulating immunosenescence and its contribution to oxi-inflamm-aging.

scholarly journals FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rawshan Choudhury ◽  
Nadhim Bayatti ◽  
Richard Scharff ◽  
Ewa Szula ◽  
Viranga Tilakaratna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Retinal Pigment ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Rpe Cells ◽  
Age Related

AbstractRetinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6, CRYAB, HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals The Protective Role of Sestrin2 in Atherosclerotic and Cardiac Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1200
Author(s):  
Yoshimi Kishimoto ◽  
Kazuo Kondo ◽  
Yukihiko Momiyama
Keyword(s):  
Oxidative Stress ◽  
Protective Role ◽  
Chronic Inflammatory Disease ◽  
Atherosclerotic Disease ◽  
Cardiac Diseases ◽  
Compensatory Response ◽  
Age Related ◽  
Anti Oxidant ◽  
Progression Of Atherosclerosis

Atherosclerotic disease, such as coronary artery disease (CAD), is known to be a chronic inflammatory disease, as well as an age-related disease. Excessive oxidative stress produced by reactive oxygen species (ROS) contributes to the pathogenesis of atherosclerosis. Sestrin2 is an anti-oxidant protein that is induced by various stresses such as hypoxia, DNA damage, and oxidative stress. Sestrin2 is also suggested to be associated with aging. Sestrin2 is expressed and secreted mainly by macrophages, endothelial cells, and cardiomyocytes. Sestrin2 plays an important role in suppressing the production and accumulation of ROS, thus protecting cells from oxidative damage. Since sestrin2 is reported to have anti-oxidant and anti-inflammatory properties, it may play a protective role against the progression of atherosclerosis and may be a potential therapeutic target for the amelioration of atherosclerosis. Regarding the association between blood sestrin2 levels and atherosclerotic disease, the blood sestrin2 levels in patients with CAD or carotid atherosclerosis were reported to be high. High blood sestrin2 levels in patients with such atherosclerotic disease may reflect a compensatory response to increased oxidative stress and may help protect against the progression of atherosclerosis. This review describes the protective role of sestrin2 against the progression of atherosclerotic and cardiac diseases.

Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

2021 ◽  
Vol 162 (33) ◽  
pp. 1318-1327
Author(s):  
Tamás Halmos ◽  
Ilona Suba
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Life Expectancy ◽  
Significant Risk ◽  
Low Grade ◽  
Aging Effects ◽  
Protective Function ◽  
Beneficial Effects ◽  
Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

scholarly journals Metaflammation: Tissue-Specific Alterations of the NLRP3 Inflammasome Platform in Metabolic Syndrome

2018 ◽  
Vol 25 (11) ◽  
pp. 1294-1310 ◽  
Author(s):  
Raffaella Mastrocola ◽  
Manuela Aragno ◽  
Giuseppe Alloatti ◽  
Massimo Collino ◽  
Claudia Penna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Advanced Glycation Endproducts ◽  
Low Grade ◽  
Advanced Glycation ◽  
Added Sugars ◽  
Physiological Ageing ◽  
Glycation Endproducts ◽  
Inflammatory Status ◽  
Age Related

In the last decades, the extension of life expectancy and the increased consumption of foods rich in saturated fats and added sugars have exposed the general population to emerging health problems. The prevalence of metabolic syndrome (MS), composed of a cluster of factors as obesity, dyslipidemia, hyperglycemia, and hypertension, is rapidly increasing in industrialized and developing countries leading to precocious onset of age-related diseases. Indeed, oxidative stress, accumulation of advanced glycation endproducts, and a chronic low-grade inflammation are common features of MS and physiological ageing. In particular, the entire set of MS factors contributes to the development of an inflammatory status named metaflammation, which has been associated with activation of early innate immune response through the assembling of the multiprotein complex inflammasome. The most investigated family of inflammasome platforms is the NOD-like receptor pyridine containing (NLRP) 3, which is activated by several exogenous and endogenous stimuli, leading to the sequential cleavage of caspase-1 and IL-1β, followed by secretion of active IL-1β. We here collect the most recent findings on NLRP3 activation in MS providing evidence of its central role in disease progression and organ dysfunction in target tissues of metaflammation, in particular in cardiovascular, hepatic and renal complications, with a focus on oxidative stress and advanced glycation endproducts. A wide overview of the most promising strategies for the modulation of NLRP3 activation and related metabolic repercussions is also provided, since the finding of specific pharmacological tools is an urgent requirement to reduce the social and economic burden of MS- and elderly-associated diseases.

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