Reduced skeletal muscle expression of mitochondrial derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease.

Reduced skeletal muscle expression of mitochondrial derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease. Am J Physiol Renal Physiol. 2019 Aug 21;: Authors: Liu C, Gidlund EK, Witasp A, Qureshi AR, Söderberg M, Thorell A, Nader GA, Barany P, Stenvinkel P, von Walden F Abstract Reduced skeletal muscle expression of mitochondrial derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease Advanced chronic kidney disease (CKD) is characterized by a premature ageing phenotype of multifactorial origin. Mitochondrial dysfunction is prevalent in CKD and has been proposed as a major contributor to poor muscle function. Although mitochondrial derived peptides (MDPs) humanin and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis and glucose control, the implications of MDP in CKD are unknown. We investigated humanin and MOTS-c protein expression in skeletal muscle and serum levels in CKD 5patients and age-matched controls with normal renal function. Whereas circulating levels of humanin were increased in CKD, the local muscle expression was reduced. In contrast, MOTS-c levels were reduced in both skeletal muscle and serum in CKD. Humanin in serum correlated positively to circulating TNF levels. Reduced MDP levels in skeletal muscle were associated with lower mitochondrial density and evidence of oxidative stress. These results indicate a differential regulation of MD...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Chronic kidney disease (CKD), a chronic catabolic condition, is characterized by muscle wasting and decreased muscle endurance. Many insights into the molecular mechanisms of muscle wasting in CKD have been obtained. A persistent imbalance between protein degradation and synthesis in muscle causes muscle wasting. During muscle wasting, high levels of reactive oxygen species (ROS) and inflammatory cytokines are detected in muscle. These increased ROS and inflammatory cytokine levels induce the expression of myostatin. The myostatin binding to its receptor activin A receptor type IIB stimulates the expressi...
Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Contributors : Chung Ki Wung ; Dhillon Poonam ; Sheng Xin ; Susztak KatalinSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusFibrosis of the kidney is the final common pathway leading to end stage renal failure. By analyzing kidneys of patients and animal models with fibrosis we observed a significant mitochondrial defect, including the loss of the mitochondrial transcription factor A (TFAM) in kidney tubule cells. Here, we generated mice with tubule-specific deletion of TFAM (Ksp-Cre/Tfam flox/flox). While these mice developed severe mitochondrial loss and energetic deficit (ATP level ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Abstract Fibrosis is the final common pathway leading to end-stage renal failure. By analyzing the kidneys of patients and animal models with fibrosis, we observed a significant mitochondrial defect, including the loss of the mitochondrial transcription factor A (TFAM) in kidney tubule cells. Here, we generated mice with tubule-specific deletion of TFAM (Ksp-Cre/Tfamflox/flox). While these mice developed severe mitochondrial loss and energetic deficit by 6 weeks of age, kidney fibrosis, immune cell infiltration, and progressive azotemia causing death were only observed around 12 weeks of age. In renal ce...
Source: Cell Metabolism - Category: Cytology Authors: Tags: Cell Metab Source Type: research
Abstract Obesity, as well as the metabolic syndrome, are well known risk factors for chronic kidney disease (CKD), but less is known about the mechanism(s) by which metabolic syndrome might accelerate kidney disease. We hypothesized that metabolic syndrome should accelerate the development of kidney disease and that it might be associated with alterations in energy metabolism.We studied the pound mouse (which develops early metabolic syndrome due to a leptin receptor deletion) and wild type littermates and compared the level of renal injury and muscle wasting following equivalent injury with oral adenine. Renal fu...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, we have identified a potential combination therapy for progressive renal fibrosis which operates, in part, through modifying mitochondrial function.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract BACKGROUND: An epidemic of chronic kidney disease of unknown etiology (Mesoamerican Nephropathy) has emerged in hot regions of Central America. We have demonstrated that dehydration associated with recurrent heat exposure causes chronic kidney disease in animal models. However, the independent influence of the core body temperature to kidney injury has not been explored. Here we tested the hypothesis that kidney injury could be accelerated by increasing body temperature independent of external temperature. METHODS: Wild type mice were exposed heat (39.5°C, 30 min, 2 times daily) with or without t...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research
In this study we show, for the first time, significant alterations in cholesterol efflux capacity in adolescents throughout the range of BMI, a relationship between six circulating adipocyte-derived EVs microRNAs targeting ABCA1 and cholesterol efflux capacity, and in vitro alterations of cholesterol efflux in macrophages exposed to visceral adipose tissue adipocyte-derived EVs acquired from human subjects. These results suggest that adipocyte-derived EVs, and their microRNA content, may play a critical role in the early pathological development of ASCVD. Commentary on the Developing UK Government Position on Hea...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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