scholarly journals The Functions of PPARs in Aging and Longevity

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Adnan Erol
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Peroxisome Proliferator ◽  
Clinical Use ◽  
Age Related ◽  
Therapeutic Uses ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Peroxisome proliferator-activated receptors (PPARs) are key regulators in various age-associated pathophysiological processes related to energy metabolism and oxidative stress. A progressive rise of oxidative stress and related inflammatory reaction appears the hallmarks of the aging process and many age-related diseases. PPARs are important redox-sensitive transcription factors and their dyregulated activations seem to be major culprits for these pathological processes. Drugs targeting PPARs activity are already in widespread clinical use; however, based on these concepts, this review highlights the understanding of the role of PPARs in aging and indicates the necessary particular attention for the potential therapeutic uses of current PPAR agonists in age-associated diseases.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Role of Peroxisome Proliferator-Activated Receptorγin Ocular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Su Zhang ◽  
Hongwei Gu ◽  
Nan Hu
Keyword(s):  
Oxidative Stress ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physiological Processes ◽  
Age Related ◽  
Potential Benefits ◽  
And Oxidative Stress

Peroxisome proliferator-activated receptorγ(PPARγ), a member of the nuclear receptor superfamily, is a ligand-activated transcription factor that plays an important role in the control of a variety of physiological processes. The last decade has witnessed an increasing interest for the role played by the agonists of PPARγin antiangiogenesis, antifibrosis, anti-inflammation effects and in controlling oxidative stress response in various organs. As the pathologic mechanisms of major blinding diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR), keratitis, and optic neuropathy, often involve neoangiogenesis and inflammation- and oxidative stress-mediated cell death, evidences are accumulating on the potential benefits of PPARγto improve or prevent these vision threatening eye diseases. In this paper we describe what is known about the role of PPARγin the ocular pathophysiological processes and PPARγagonists as novel adjuvants in the treatment of eye diseases.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

scholarly journals Role of Klotho in Chronic Calcineurin Inhibitor Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Kang Luo ◽  
Sun Woo Lim ◽  
Yi Quan ◽  
Sheng Cui ◽  
Yoo Jin Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Calcineurin Inhibitor ◽  
Calcineurin Inhibitors ◽  
Common Mechanism ◽  
Protective Mechanism ◽  
Klotho Protein ◽  
The Common ◽  
And Oxidative Stress

Calcineurin inhibitors (CNIs) are the most popular immunosuppressants in organ transplantation, but nephrotoxicity is a major concern. The common mechanism underlying chronic CNI nephropathy is oxidative stress, and the process of chronic CNI nephropathy is similar to that of aging. Current studies provide evidence that antiaging Klotho protein plays an important role in protecting against oxidative stress, and its signaling is a target for preventing oxidative stress-induced aging process. In this review, we focus on the association between Klotho and oxidative stress and the protective mechanism of action of Klotho against oxidative stress in chronic CNI nephropathy. In addition, we discuss the delivery strategy for Klotho in CNI-induced nephropathy.

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 New Insights into the Role of Peroxisome Proliferator-Activated Receptors in Regulating the Inflammatory Response after Tissue Injury

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Miriam D. Neher ◽  
Sebastian Weckbach ◽  
Markus S. Huber-Lang ◽  
Philip F. Stahel
Keyword(s):  
Inflammatory Response ◽  
Major Trauma ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Healing Process ◽  
Wound Healing Process ◽  
Peroxisome Proliferator ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Major trauma results in a strong inflammatory response in injured tissue. This posttraumatic hyperinflammation has been implied in the adverse events leading to a breakdown of host defense mechanisms and ultimately to delayed organ failure. Ligands to peroxisome proliferator-activated receptors (PPARs) have recently been identified as potent modulators of inflammation in various acute and chronic inflammatory conditions. The main mechanism of action mediated by ligand binding to PPARs is the inhibition of the nuclear transcription factor NF-κB, leading to downregulation of downstream gene transcription, such as for genes encoding proinflammatory cytokines. Pharmacological PPAR agonists exert strong anti-inflammatory properties in various animal models of tissue injury, including central nervous system trauma, ischemia/reperfusion injury, sepsis, and shock. In addition, PPAR agonists have been shown to induce wound healing process after tissue trauma. The present review was designed to provide an up-to-date overview on the current understanding of the role of PPARs in the pathophysiology of the inflammatory response after major trauma. Therapeutic options for using recombinant PPAR agonists as pharmacological agents in the management of posttraumatic inflammation will be discussed.

scholarly journals PPAR and Oxidative Stress: Con() Catenating NRF2 and FOXO

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Simone Polvani ◽  
Mirko Tarocchi ◽  
Andrea Galli
Keyword(s):  
Oxidative Stress ◽  
Nuclear Receptor ◽  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Related Factor ◽  
Central Importance ◽  
Forkhead Box ◽  
Forkhead Box Proteins ◽  
And Oxidative Stress

Peroxisome-proliferator activator receptorγ(PPARγ) is a nuclear receptor of central importance in energy homeostasis and inflammation. Recent experimental pieces of evidence demonstrate that PPARγis implicated in the oxidative stress response, an imbalance between antithetic prooxidation and antioxidation forces that may lead the cell to apoptotic or necrotic death. In this delicate and intricate game of equilibrium, PPARγstands out as a central player devoted to the quenching and containment of the damage and to foster cell survival. However, PPARγdoes not act alone: indeed the nuclear receptor is at the point of interconnection of various pathways, such as the nuclear factor erythroid 2-related factor 2 (NRF2), Wnt/β-catenin, and forkhead box proteins O (FOXO) pathways. Here we reviewed the role of PPARγin response to oxidative stress and its interaction with other signaling pathways implicated in this process, an interaction that emerged as a potential new therapeutic target for several oxidative-related diseases.

scholarly journals Enhanced Hepatocarcinogenicity Due to Agonists of Peroxisome Proliferator-Activated Receptors in Senescent Rats: Role of Peroxisome Proliferation, Cell Proliferation, and Apoptosis

2002 ◽  
Vol 2 ◽  
pp. 1491-1500 ◽  
Author(s):  
Jihan Youssef ◽  
Mostafa Badr
Keyword(s):  
Cell Proliferation ◽  
Peroxisome Proliferator ◽  
Carcinogenic Effect ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Findings ◽  
Proliferation And Apoptosis ◽  
Ppar Agonists ◽  
Old Rats ◽  
Peroxisome Proliferator Activated Receptors

Exposure to agonists of peroxisome proliferator-activated receptor alpha (PPARα) causes liver cancer in rodents, with aged animals being more susceptible than their younger counterparts to this effect. Treatment with these chemicals produced a five- to sevenfold higher yield of grossly visible hepatic tumors in old rats compared to young animals. The enhanced susceptibility of the aged livers to the carcinogenic effect of PPAR agonists could not be explained by differences in levels of peroxisomal and/or cell proliferation between young and old animals, as neither of these responses was exaggerated with aging. Reported studies have shown that activating PPARa results in the suppression of hepatic apoptosis. This effect is expected to diminish the ability of the liver to purge itself of pre-existing neoplastic cells, allowing them to progress to tumors. New findings from our laboratories show that the aged liver is exceedingly sensitive to the antiapoptotic effect of PPAR agonists. In addition, aged livers showed remarkably higher levels of the antiapoptotic protein Bcl-2 than livers of young, adult, and middle-aged animals. Interestingly, the PPARa agonist Wy-14,643 significantly diminished elements of the proapoptotic machinery (e.g., Bax, caspases, and fas) in the aged liver, while remarkably increasing elements of this machinery in younger animals. Taken together, while activation of PPARs appears to inhibit apoptosis in livers of senescent animals, activating these receptors seems to stimulate the apoptotic machinery in young animals. This paradoxical effect may be responsible for the exaggerated sensitivity of the aged liver to the carcinogenic effect of agents that activate PPARs.

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