scholarly journals ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Pierpaola Davalli ◽  
Tijana Mitic ◽  
Andrea Caporali ◽  
Angela Lauriola ◽  
Domenico D’Arca
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
Cell Senescence ◽  
Therapeutic Interventions ◽  
Causal Connection ◽  
Oxygen Species ◽  
The Novel ◽  
Age Related ◽  
Multiple Levels ◽  
Stress Damage

The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS). Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

scholarly journals Fighting Oxidative Stress with Sulfur: Hydrogen Sulfide in the Renal and Cardiovascular Systems

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 373
Author(s):  
Joshua J. Scammahorn ◽  
Isabel T. N. Nguyen ◽  
Eelke M. Bos ◽  
Harry Van Goor ◽  
Jaap A. Joles
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Redox Status ◽  
The Body ◽  
Therapeutic Interventions ◽  
Oxygen Species ◽  
Enzymatic Production ◽  
Age Related ◽  
Anti Oxidant ◽  
Enzymatic Pathways

Hydrogen sulfide (H2S) is an essential gaseous signaling molecule. Research on its role in physiological and pathophysiological processes has greatly expanded. Endogenous enzymatic production through the transsulfuration and cysteine catabolism pathways can occur in the kidneys and blood vessels. Furthermore, non-enzymatic pathways are present throughout the body. In the renal and cardiovascular system, H2S plays an important role in maintaining the redox status at safe levels by promoting scavenging of reactive oxygen species (ROS). H2S also modifies cysteine residues on key signaling molecules such as keap1/Nrf2, NFκB, and HIF-1α, thereby promoting anti-oxidant mechanisms. Depletion of H2S is implicated in many age-related and cardiorenal diseases, all having oxidative stress as a major contributor. Current research suggests potential for H2S-based therapies, however, therapeutic interventions have been limited to studies in animal models. Beyond H2S use as direct treatment, it could improve procedures such as transplantation, stem cell therapy, and the safety and efficacy of drugs including NSAIDs and ACE inhibitors. All in all, H2S is a prime subject for further research with potential for clinical use.

scholarly journals Placental Vacuolar ATPase Function Is a Key Link between Multiple Causes of Preeclampsia

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Dongxin Zhang ◽  
Duyun Ye ◽  
Hongxiang Chen
Keyword(s):  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Vacuolar Atpase ◽  
Therapeutic Interventions ◽  
The Novel ◽  
Lipoxin A4 ◽  
Angiotensin System ◽  
Dihydroxyvitamin D ◽  
System 1 ◽  
Multiple Causes

Preeclampsia, a relatively common pregnancy disorder, is one of the major causes of maternal and fetal morbidity and mortality. Despite numerous research, the etiology of this syndrome remains not well understood as the pathogenesis of preeclampsia is complex, involving interaction between genetic, immunologic, and environmental factors. Preeclampsia, originating in placenta abnormalities, is induced by the circulating factors derived from the abnormal placenta. Recent work has identified various molecular mechanisms related to placenta development, including renin-angiotensin system, 1, 25-dihydroxyvitamin D, and lipoxin A4. Interestingly, advances suggest that vacuolar ATPase, a key molecule in placentation, is closely associated with them. Therefore, this intriguing molecule may represent an important link between various causes of preeclampsia. Here, we review that vacuolar ATPase works as a key link between multiple causes of preeclampsia and discuss the potential molecular mechanisms. The novel findings outlined in this review may provide promising explanations for the causation of preeclampsia and a rationale for future therapeutic interventions for this condition.

scholarly journals Senescence and aging: Causes, consequences, and therapeutic avenues

2017 ◽  
Vol 217 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Domhnall McHugh ◽  
Jesús Gil
Keyword(s):  
Neurodegenerative Disorders ◽  
Cellular Response ◽  
Aging Process ◽  
Normal Development ◽  
Growth Arrest ◽  
The Novel ◽  
Aging Research ◽  
Related Disease ◽  
Age Related ◽  
Stable Growth

Aging is the major risk factor for cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. Although we are far from understanding the biological basis of aging, research suggests that targeting the aging process itself could ameliorate many age-related pathologies. Senescence is a cellular response characterized by a stable growth arrest and other phenotypic alterations that include a proinflammatory secretome. Senescence plays roles in normal development, maintains tissue homeostasis, and limits tumor progression. However, senescence has also been implicated as a major cause of age-related disease. In this regard, recent experimental evidence has shown that the genetic or pharmacological ablation of senescent cells extends life span and improves health span. Here, we review the cellular and molecular links between cellular senescence and aging and discuss the novel therapeutic avenues that this connection opens.

Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

2007 ◽  
Vol 32 (5) ◽  
pp. 954-966 ◽  
Author(s):  
Christy S. Carter ◽  
Tim Hofer ◽  
Arnold Y. Seo ◽  
Christian Leeuwenburgh
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
Geriatric Medicine ◽  
Functional Decline ◽  
Intervention Strategies ◽  
Health Span ◽  
Structural Deterioration ◽  
Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

scholarly journals A panel of clinical and neuropathological features of cerebrovascular disease through the novel neuroimaging methods

2017 ◽  
Vol 11 (4) ◽  
pp. 343-355 ◽  
Author(s):  
Gilberto Sousa Alves ◽  
Luiza de Amorim de Carvalho ◽  
Felipe Kenji Sudo ◽  
Lucas Briand ◽  
Jerson Laks ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Small Vessel Disease ◽  
Scientific Information ◽  
Vascular Cognitive Impairment ◽  
Diagnostic Workup ◽  
Therapeutic Interventions ◽  
Vascular Lesions ◽  
The Novel ◽  
Age Related ◽  
Positron Emission

ABSTRACT. The last decade has witnessed substantial progress in acquiring diagnostic biomarkers for the diagnostic workup of cerebrovascular disease (CVD). Advanced neuroimaging methods not only provide a strategic contribution for the differential diagnosis of vascular dementia (VaD) and vascular cognitive impairment (VCI), but also help elucidate the pathophysiological mechanisms ultimately leading to small vessel disease (SVD) throughout its course. Objective: In this review, the novel imaging methods, both structural and metabolic, were summarized and their impact on the diagnostic workup of age-related CVD was analysed. Methods: An electronic search between January 2010 and 2017 was carried out on PubMed/MEDLINE, Institute for Scientific Information Web of Knowledge and EMBASE. Results: The use of full functional multimodality in simultaneous Magnetic Resonance (MR)/Positron emission tomography (PET) may potentially improve the clinical characterization of VCI-VaD; for structural imaging, MRI at 3.0 T enables higher-resolution scanning with greater imaging matrices, thinner slices and more detail on the anatomical structure of vascular lesions. Conclusion: Although the importance of most of these techniques in the clinical setting has yet to be recognized, there is great expectancy in achieving earlier and more refined therapeutic interventions for the effective management of VCI-VaD.

scholarly journals Potential Therapeutic Candidates for Age-Related Macular Degeneration (AMD)

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2483
Author(s):  
Sonali Nashine
Keyword(s):  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Vascular Inflammation ◽  
Retinal Pigment ◽  
The United States ◽  
Age Related Macular Degeneration ◽  
Therapeutic Interventions ◽  
Oxygen Species ◽  
Ocular Diseases ◽  
Age Related

Aging contributes to the risk of development of ocular diseases including, but not limited to, Age-related Macular Degeneration (AMD) that is a leading cause of blindness in the United States as well as worldwide. Retinal aging, that contributes to AMD pathogenesis, is characterized by accumulation of drusen deposits, alteration in the composition of Bruch’s membrane and extracellular matrix, vascular inflammation and dysregulation, mitochondrial dysfunction, and accumulation of reactive oxygen species (ROS), and subsequent retinal pigment epithelium (RPE) cell senescence. Since there are limited options available for the prophylaxis and treatment of AMD, new therapeutic interventions are constantly being looked into to identify new therapeutic targets for AMD. This review article discusses the potential candidates for AMD therapy and their known mechanisms of cytoprotection in AMD. These target therapeutic candidates include APE/REF-1, MRZ-99030, Ciliary NeuroTrophic Factor (CNTF), RAP1 GTPase, Celecoxib, and SS-31/Elamipretide.

scholarly journals Regulation of Autophagy in Aging and Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 743-744
Author(s):  
Malene Hansen
Keyword(s):  
Molecular Mechanisms ◽  
Molecular Level ◽  
Recycling Process ◽  
Cellular Homeostasis ◽  
C Elegans ◽  
Age Related ◽  
Multiple Levels ◽  
Critical Process

Abstract The cytosolic recycling process of autophagy plays an important role in many age-related diseases and has been directly linked to aging, including in the nematode C. elegans where autophagy appears beneficially induced in many conserved longevity models. As a critical process to ensure cellular homeostasis, autophagy is regulated at multiple levels, yet it remains a challenge in the field to understand how the regulation of autophagy is integrated at the cellular and molecular level to ensure health- and lifespan benefits. I will here discuss our progress on understanding the different molecular mechanisms employed by cells and organisms to regulate autophagy in response to stressors such as aging and disease.

scholarly journals Proteome and Secretome Dynamics of Stem Cell-Derived Retinal Pigmented Epithelium in Response to Acute and Chronic ROS

2019 ◽  
Author(s):  
Jesse G. Meyer ◽  
Thelma Garcia ◽  
Birgit Schilling ◽  
Bradford W. Gibson ◽  
Deepak A. Lamba
Keyword(s):  
Reactive Oxygen Species ◽  
Stem Cell ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Urotensin Ii ◽  
Retinal Pigmented Epithelium ◽  
Age Related ◽  
Pigmented Epithelium

AbstractAge-related macular degeneration (AMD) is the leading cause of blindness in developed countries, and is characterized by slow retinal degeneration linked to chronic oxidative stress in the retinal pigmented epithelium (RPE). The exact molecular mechanisms that lead to RPE death and dysfunction in response to chronic reactive oxygen species (ROS) are still unclear. In this work, human stem cell-derived RPE samples were treated with a low dose of paraquat (PQ) for 1 week or 3 weeks to induce chronic reactive oxygen species (ROS) stress. Cells were then harvested and both the intracellular and secreted RPE proteomes were quantified by mass spectrometry. Inside the RPE, chronic ROS caused concerted increase of glycolytic proteins but decreased mitochondrial proteins, as well as decreased extracellular matrix proteins and membrane proteins required for endocytosis. From the secreted proteins, we found that stressed RPE secrete over 1,000 detectable proteins, and the composition of the proteins secreted from RPE changes due to chronic ROS. Notably, secreted APOE is decreased 4-fold due to 3 weeks of chronic ROS stress, and urotensin-II, the strongest known vasoconstrictor, doubles. Further, secreted TGF-beta is increased, and its cognate signaler BMP1 decreased in the secretome. Together, these alterations of the RPE proteome and protein secretome paint a detailed molecular picture of the retinal stress response in space and time.

scholarly journals Emerging roles of extracellular vesicles in the intercellular communication for exercise-induced adaptations

2020 ◽  
Vol 319 (2) ◽  
pp. E320-E329
Author(s):  
Joshua Denham ◽  
Sarah J. Spencer
Keyword(s):  
Extracellular Vesicles ◽  
Intercellular Communication ◽  
Biological Material ◽  
Molecular Mechanisms ◽  
Health Benefits ◽  
Extracellular Vesicle ◽  
Therapeutic Interventions ◽  
Current Evidence ◽  
Future Research ◽  
Age Related

Complex organisms rely heavily on intercellular communication. The rapidly expanding field of extracellular vesicle biology has made it clear that the necessary intercellular communication occurs partly through their paracrine and endocrine actions. Extracellular vesicles are nanoscale lipid membranes (30–2,000 nm in diameter) that shuttle functional biological material between cells. They are released from numerous tissues and are isolated from nearly all biofluids and cell cultures. Although their biogenesis, cell targeting, and functional roles are incompletely understood, they appear to have crucial roles in physiological and disease processes. Their enormous potential to serve as sensitive biomarkers of disease and also new therapeutic interventions for diseases have gained them considerable attention in recent years. Regular physical exercise training confers systemic health benefits and consequently prevents many age-related degenerative diseases. Many of the molecular mechanisms responsible for the salubrious effects of exercise are known, yet a common underlying mechanism potentially responsible for the holistic health benefits of exercise has only recently been explored (i.e., via extracellular vesicle transport of biological material). Here, we provide an overview of extracellular vesicle biology before outlining the current evidence on the capacity for a single bout and chronic exercise to elicit changes in extracellular vesicle content and modulate their molecular cargo (e.g., small RNAs). We highlight areas for future research and emphasize their potential utility as biomarkers and therapeutic strategies of disease and its prevention.

scholarly journals The Protective Effect of Lipoic Acid on Selected Cardiovascular Diseases Caused by Age-Related Oxidative Stress

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Beata Skibska ◽  
Anna Goraca
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Lipoic Acid ◽  
Aging Process ◽  
Antioxidant Defense ◽  
Ros Production ◽  
Oxygen Species ◽  
Oxidative Stress Parameters ◽  
Age Related ◽  
Stress Parameters

Oxidative stress is considered to be the primary cause of many cardiovascular diseases, including endothelial dysfunction in atherosclerosis and ischemic heart disease, hypertension, and heart failure. Oxidative stress increases during the aging process, resulting in either increased reactive oxygen species (ROS) production or decreased antioxidant defense. The increase in the incidence of cardiovascular disease is directly related to age. Aging is also associated with oxidative stress, which in turn leads to accelerated cellular senescence and organ dysfunction. Antioxidants may help lower the incidence of some pathologies of cardiovascular diseases and have antiaging properties. Lipoic acid (LA) is a natural antioxidant which is believed to have a beneficial effect on oxidative stress parameters in relation to diseases of the cardiovascular system.

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