scholarly journals Sirtuins and renal diseases: relationship with aging and diabetic nephropathy

2012 ◽  
Vol 124 (3) ◽  
pp. 153-164 ◽  
Author(s):  
Munehiro Kitada ◽  
Shinji Kume ◽  
Ai Takeda-Watanabe ◽  
Keizo Kanasaki ◽  
Daisuke Koya
Keyword(s):  
Diabetic Nephropathy ◽  
Redox State ◽  
Sodium Balance ◽  
Renal Diseases ◽  
Class Iii ◽  
Causal Factors ◽  
Cellular Energy ◽  
Age Related ◽  
Survival Pathways ◽  
Regulate Lipid Metabolism

Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1–SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

scholarly journals Renal Protective Effect of Sirtuin 1

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yi-jun Dong ◽  
Nian Liu ◽  
Zhi Xiao ◽  
Tao Sun ◽  
Shu-hui Wu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Sirtuin 1 ◽  
Acute Renal Injury ◽  
Cellular Energy ◽  
The Past ◽  
Age Related ◽  
Survival Pathways

Silent information regulator 2 (Sir2) is a nicotinamide adenine dinucleotide- (NAD+-) dependent deacetylase. The homology of SIRT1 and Sir2 has been extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. During the past decade, investigators have reported that SIRT1 activity is essential in cancer, neurodegenerative diseases, diabetes, cardiovascular disease, and other age-related diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation, and fibrosis. Therefore its activation may also become a new therapeutic target in the patients with chronic kidney disease including diabetic nephropathy. In this paper, we would like to review the protective functions of sirtuins and the role of SIRT1 in the onset of kidney disease based on previous studies, including diabetic nephropathy, acute renal injury, chronic kidney disease as well as lupus nephritis.

scholarly journals mTOR Signaling in the Inner Ear as Potential Target to Treat Hearing Loss

2021 ◽  
Vol 22 (12) ◽  
pp. 6368
Author(s):  
Maurizio Cortada ◽  
Soledad Levano ◽  
Daniel Bodmer
Keyword(s):  
Hearing Loss ◽  
Cell Survival ◽  
Inner Ear ◽  
Hearing Aids ◽  
Noise Exposure ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Curative Therapy ◽  
Age Related ◽  
Survival Pathways

Hearing loss affects many people worldwide and occurs often as a result of age, ototoxic drugs and/or excessive noise exposure. With a growing number of elderly people, the number of people suffering from hearing loss will also increase in the future. Despite the high number of affected people, for most patients there is no curative therapy for hearing loss and hearing aids or cochlea implants remain the only option. Important treatment approaches for hearing loss include the development of regenerative therapies or the inhibition of cell death/promotion of cell survival pathways. The mammalian target of rapamycin (mTOR) pathway is a central regulator of cell growth, is involved in cell survival, and has been shown to be implicated in many age-related diseases. In the inner ear, mTOR signaling has also started to gain attention recently. In this review, we will emphasize recent discoveries of mTOR signaling in the inner ear and discuss implications for possible treatments for hearing restoration.

Ageing and the human brain

2020 ◽  
pp. 170-182
Author(s):  
Verena Heise ◽  
Enikő Zsoldos ◽  
Klaus P. Ebmeier
Keyword(s):  
In Vivo Imaging ◽  
Allostatic Load ◽  
Public Health Medicine ◽  
Causal Factors ◽  
Stress Markers ◽  
Age Related ◽  
Brain Changes ◽  
Heuristic Device ◽  
The Brain

There is little doubt that the brain changes with time, and all research in psychiatry is predicated on holding age constant in comparing groups of patients or estimating the effect sizes of causal factors. Nevertheless, relatively little is known about the mechanisms that are responsible for translating time into ageing. This chapter tries, after an overview of the principal mechanisms involved in biological ageing, to summarize the age-related changes observable in brains in vivo and to demonstrate the types of investigations that may cast light on such mechanisms in the future. A useful heuristic device to order the multiple potential causes of ageing is the chronic stress–allostatic load model, widely employed in epidemiology, public health medicine, and health psychology. In vivo imaging provides a method to test the translation of intermediate stress markers, such as vascular risk, metabolic syndrome, or allostatic load, into predictors of age-related brain changes.

Age-related changes in plasma coenzyme Q10 concentrations and redox state in apparently healthy children and adults

2004 ◽  
Vol 347 (1-2) ◽  
pp. 139-144 ◽  
Author(s):  
Michael V Miles ◽  
Paul S Horn ◽  
Peter H Tang ◽  
John A Morrison ◽  
Lili Miles ◽  
...  
Keyword(s):  
Coenzyme Q10 ◽  
Redox State ◽  
Healthy Children ◽  
Age Related ◽  
Age Related Changes ◽  
Apparently Healthy

scholarly journals The Common FTO Genetic Polymorphism rs9939609 is Associated with Increased BMI in Type 1 Diabetes but not with Diabetic Nephropathy

2010 ◽  
Vol 5 ◽  
pp. BMI.S4599 ◽  
Author(s):  
Harvest F. Gu ◽  
Alexandra Alvarsson ◽  
Kerstin Brismar
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Genetic Polymorphism ◽  
Kidney Diseases ◽  
Renal Diseases ◽  
Allelic Association ◽  
Fto Gene ◽  
The Common ◽  
Diabetes Patients

The fat mass and obesity associated (FTO) gene has an important genetic effect on body mass index (BMI) and risk of obesity, and obesity contributes to the progression of renal diseases, including diabetic nephropathy. We thus conducted a genetic association study to evaluate whether the FTO gene confers the risk susceptibility to the development of diabetic nephropathy. Genotyping experiments of the common FTO polymorphism, rs9939609, in 1170 type 1 diabetes patients with (n = 597) or without diabetic nephropathy (n = 573) were performed with TaqMan allelic discrimination. All subjects are of European descent and selected from the Genetics of Kidney Diseases in Diabetes (GoKinD) study. The frequency of T allele of this polymorphism was 0.414 in the studied population. There was no allelic association of this polymorphism with diabetic nephropathy. But, the risk susceptibility of A allele conferring to the increased BMI among type 1 diabetes patients was observed. The subjects carrying with AA genotype had higher BMI compared to the carriers with TA and/or TT genotype(s) ( P ≥ 0.019). The present study provides evidence that the common FTO genetic polymorphism, rs9939609, is associated with increased BMI in type 1 diabetes but not with diabetic nephropathy.

scholarly journals Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

2020 ◽  
Vol 9 (1) ◽  
pp. 272 ◽  
Author(s):  
Carolina Lavoz ◽  
Sandra Rayego-Mateos ◽  
Macarena Orejudo ◽  
Lucas Opazo-Ríos ◽  
Vanessa Marchant ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Immune Cells ◽  
Current Knowledge ◽  
Premature Mortality ◽  
Active Role ◽  
Renal Diseases ◽  
Economic Implications ◽  
Number Of Patients ◽  
Stage Renal Disease

Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

scholarly journals Radiographic assessment of lower third molar eruption in different anteroposterior skeletal patterns and age-related groups

2014 ◽  
Vol 85 (4) ◽  
pp. 577-584 ◽  
Author(s):  
Aleksandar Jakovljevic ◽  
Emira Lazic ◽  
Ivan Soldatovic ◽  
Nenad Nedeljkovic ◽  
Miroslav Andric
Keyword(s):  
Logistic Regression ◽  
Age Groups ◽  
Third Molar ◽  
Width Ratio ◽  
Class Iii ◽  
Second Molar ◽  
Age Related ◽  
Mandibular Third Molar ◽  
Lateral Cephalograms ◽  
Third Molar Eruption

ABSTRACT Objective:  To analyze radiographic predictors for lower third molar eruption among subjects with different anteroposterior skeletal relations and of different age groups. Materials and Methods:  In total, 300 lower third molars were recorded on diagnostic digital orthopantomograms (DPTs) and lateral cephalograms (LCs). The radiographs were grouped according to sagittal intermaxillary angle (ANB), subject age, and level of lower third molar eruption. The DPT was used to analyze retromolar space, mesiodistal crown width, space/width ratio, third and second molar angulation (α, γ), third molar inclination (β), and gonion angle. The LC was used to determine ANB, angles of maxillar and mandibular prognathism (SNA, SNB), mandibular plane angle (SN/MP), and mandibular lengths. A logistic regression model was created using the statistically significant predictors. Results:  The logistic regression analysis revealed a statistically significant impact of β angle and distance between gonion and gnathion (Go-Gn) on the level of lower third molar eruption (P < .001 and P < .015, respectively). The retromolar space was significantly increased in the adult subgroup for all skeletal classes. The lower third molar impaction rate was significantly higher in the adult subgroup with the Class II (62.3%) compared with Class III subjects (31.7%; P < .013). Conclusion:  The most favorable values of linear and angular predictors of mandibular third molar eruption were measured in Class III subjects. For valid estimation of mandibular third molar eruption, certain linear and angular measures (β angle, Go-Gn), as well as the size of the retromolar space, need to be considered.

Suppressions of chronic glomerular injuries and TGF-β1 production by HGF in attenuation of murine diabetic nephropathy

2004 ◽  
Vol 286 (1) ◽  
pp. F134-F143 ◽  
Author(s):  
Shinya Mizuno ◽  
Toshikazu Nakamura
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Renal Dysfunction ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Renal Diseases ◽  
Glomerular Mesangial Cells ◽  
Diabetic Mice

Diabetic nephropathy is now the leading cause of end-stage renal diseases, and glomerular sclerotic injury is an initial event that provokes renal dysfunction during processes of diabetes-linked kidney disease. Growing evidence shows that transforming growth factor-β1 (TGF-β1) plays a key role in this process, especially in eliciting hypertrophy and matrix overaccumulation. Thus it is important to find a ligand system to antagonize the TGF-β1-mediated pathogenesis under high-glucose conditions. Herein, we provide evidence that hepatocyte growth factor (HGF) targets mesangial cells, suppresses TGF-β1 production, and minimizes glomerular sclerotic changes, using streptozotocin-induced diabetic mice. In our murine model, glomerular sclerogenesis (such as tuft area expansion and collagen deposition) progressed between 6 and 10 wk after the induction of hyperglycemia, during a natural course of diabetic disease. Glomerular HGF expression levels in the diabetic kidney transiently increased but then declined below a basal level, with manifestation of glomerular sclerogenesis. When anti-HGF IgG was injected into mice for 2 wk (i.e., from weeks 4 to 6 after onset of hyperglycemia), these glomerular changes were significantly aggravated. When recombinant HGF was injected into the mice for 4 wk (i.e., between 6 and 10 wk following streptozotocin treatment), the progression of glomerular hypertrophy and sclerosis was almost completely inhibited, even though glucose levels remained unchanged (>500 mg/dl). Even more important, HGF repressed TGF-β1 production in glomerular mesangial cells even under hyperglycemic conditions both in vitro and in vivo. Consequently, not only albuminuria but also tubulointerstitial fibrogenesis were attenuated by HGF. Overall, HGF therapy inhibited the onset of renal dysfunction in the diabetic mice. On the basis of these findings, we wish to emphasize that HGF plays physiological and therapeutic roles in blocking renal fibrogenesis during a course of diabetic nephropathy.

In vivo monitoring of cellular energy metabolism using SoNar, a highly responsive sensor for NAD+/NADH redox state

2016 ◽  
Vol 11 (8) ◽  
pp. 1345-1359 ◽  
Author(s):  
Yuzheng Zhao ◽  
Aoxue Wang ◽  
Yejun Zou ◽  
Ni Su ◽  
Joseph Loscalzo ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Redox State ◽  
Cellular Energy ◽  
In Vivo Monitoring ◽  
Cellular Energy Metabolism ◽  
Nadh Redox State

scholarly journals Novel Role of Parathyroid Hormone-Related Protein in the Pathophysiology of the Diabetic Kidney: Evidence from Experimental and Human Diabetic Nephropathy

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Montserrat Romero ◽  
Arantxa Ortega ◽  
Nuria Olea ◽  
María Isabel Arenas ◽  
Adriana Izquierdo ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Parathyroid Hormone ◽  
Renal Injury ◽  
Renal Diseases ◽  
Protective Effects ◽  
Ang Ii ◽  
Related Protein ◽  
Renal Hypertrophy ◽  
Glomerular Diseases ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1R) are extensively expressed in the kidney, where they are able to modulate renal function. Renal PTHrP is known to be overexpressed in acute renal injury. Recently, we hypothesized that PTHrP involvement in the mechanisms of renal injury might not be limited to conditions with predominant damage of the renal tubulointerstitium and might be extended to glomerular diseases, such as diabetic nephropathy (DN). In experimental DN, the overexpression of both PTHrP and the PTH1R contributes to the development of renal hypertrophy as well as proteinuria. More recent data have shown, for the first time, that PTHrP is upregulated in the kidney from patients with DN. Collectively, animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a mechanism which involves the modulation of cell cycle regulatory proteins and TGF-β1. Furthermore, angiotensin II (Ang II), a critical factor in the progression of renal injury, appears to be responsible for PTHrP upregulation in these conditions. These findings provide novel insights into the well-known protective effects of Ang II antagonists in renal diseases, paving the way for new therapeutic approaches.

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