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Klotho

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https://www.readbyqxmd.com/read/28431289/klotho-apoe%C3%AE%C2%B54-cognitive-ability-brain-size-atrophy-and-survival-a-study-in-the-aberdeen-birth-cohort-of-1936
#1
Clarisse F de Vries, Roger T Staff, Sarah E Harris, Dorota Chapko, Daniel S Williams, Polina Reichert, Trevor Ahearn, Christopher J McNeil, Lawrence J Whalley, Alison D Murray
A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition, and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show that, relative to noncarriers, KL-VS heterozygotes had (1) shorter survival; (2) smaller white matter volumes; (3) slower cognitive decline; and (4) greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected...
March 7, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28429560/is-there-a-role-for-newer-biomarkers-in-chronic-kidney-disease-mineral-and-bone-disorder-management
#2
Sven-Jean Tan, Michael Mx Cai
The current management of Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD) relies largely on clinical judgement and assessment of biochemical parameters including serum calcium, phosphate and intact parathyroid hormone concentrations. In the past two decades, there has been a leap in the understanding of the pathophysiology of CKD-MBD, leading to the discovery of novel biomarkers. The potential utility of these markers in this clinical setting is an area of intense investigation. In the absence of any guidelines aiding the clinician's understanding and application of these markers, we summarise the current available literature surrounding fibroblast growth factor-23, α-Klotho, sclerostin and serum calcification propensity testing and their respective assays in the context of CKD-MBD management...
March 2017: Nephrology
https://www.readbyqxmd.com/read/28428174/klotho-an-anti-aging-molecule-attenuates-oxidant-induced-alveolar-epithelial-cell-mtdna-damage-and-apoptosis
#3
Seok-Jo Kim, Paul Cheresh, Mesut Eren, Renea P Jablonski, Anjana Yeldandi, Karen M Ridge, Gr Scott Budinger, Dong-Hyun Kim, Myles S Wolf, Douglas Vaughan, David W Kamp
Alveolar epithelial cell (AEC) apoptosis and inadequate repair resulting from 'exaggerated' lung aging and mitochondrial dysfunction are critical determinants promoting lung fibrosis. α-Klotho, which is an anti-aging molecule that is expressed predominantly in the kidney and secreted in the blood, can protect lung epithelial cells against hyperoxia-induced apoptosis. We reasoned that Klotho protects AEC exposed to oxidative stress in part by maintaining mitochondrial DNA (mtDNA) integrity and mitigating apoptosis...
April 20, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#4
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28416226/klotho-restoration-via-acetylation-of-peroxisome-proliferation-activated-receptor-%C3%AE-reduces-the-progression-of-chronic-kidney-disease
#5
Wenjun Lin, Qin Zhang, Lin Liu, Shasha Yin, Zhihong Liu, Wangsen Cao
Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho (1) expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28415155/letter-to-the-editor-regarding-dounousi-e-et%C3%A2-al-intact-fgf23-and-%C3%AE-klotho-during-acute-inflammation-sepsis-in-ckd-patients-eur-j-clin-invest-2016-46-234-41
#6
Axel Schlitt, Urban Sester, Martina Sester, Sarah Seiler-Mussler, Vincent Brandenburg, Elke Schäffner, Gunnar H Heine
With interest we read the recent European Journal of Clinical Investigation paper entitled "Intact FGF23 and α-Klotho during acute inflammation/sepsis in CKD patients" by E. Dounousi and coworkers (1). In their article, the authors analyse the association between acute infection and plasma levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23). The physiological regulation of FGF-23 is not fully understood so far, and hence novel pathophysiological data are of importance. Particularly the link between FGF23 and inflammation is a growing field...
April 17, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28411025/klotho-down-regulates-egr-1-by-inhibiting-tgf-%C3%AE-1-smad3-signaling-in-high-glucose-treated-human-mesangial-cells
#7
Yang Li, Fang Hu, Meng Xue, Yi-Jie Jia, Zong-Ji Zheng, Ling Wang, Mei-Ping Guan, Yao-Ming Xue
Diabetic kidney disease (DKD) has become the leading cause of end-stage renal disease worldwide and is associated with glomerular mesangial cell (MC) proliferation and excessive extracellular matrix (ECM) production. Klotho can attenuate renal fibrosis in part by inhibiting TGF-β1/Smad3 signaling in DKD. Early growth response factor 1 (Egr-1) has been shown to play a key role in renal fibrosis in part by facilitating the formation of a positive feedback loop involving TGF-β1. However, whether Klotho down-regulates Egr-1 by inhibiting TGF-β1/Smad3 signaling in DKD is unclear...
April 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28407763/klotho-ameliorates-oxidized-low-density-lipoprotein-ox-ldl-induced-oxidative-stress-via-regulating-lox-1-and-pi3k-akt-enos-pathways
#8
Yansheng Yao, Yanbing Wang, Yibo Zhang, Chang Liu
BACKGROUND: Atherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs)...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28405606/changes-in-markers-of-mineral-metabolism-after-living-kidney-donation
#9
Sven-Jean Tan, Tim D Hewitson, Peter D Hughes, Stephen G Holt, Nigel D Toussaint
BACKGROUND: Living kidney donors (LKDs) experience reduction in kidney function, however serum phosphate (sPi) levels are lower compared to patients with chronic kidney disease matched for reduced kidney function. Mineral metabolism adaptations that occur in LKDs have not been adequately investigated. To evaluate the effect of nephrectomy on markers of mineral metabolism in LKDs compared to healthy volunteers (HV) over 12 months. METHODS: Mineral parameters were evaluated in twenty-one adult LKDs and twenty HVs...
April 2017: Transplantation Direct
https://www.readbyqxmd.com/read/28402487/circulating-klotho-associates-with-cardiovascular-morbidity-and-mortality-during-hemodialysis
#10
Christophe Marçais, Delphine Maucort-Boulch, Jocelyne Drai, Emmanuelle Dantony, Marie-Christine Carlier, Emilie Blond, Leslie Genet, François Kuentz, Dominique Lataillade, Eric Legrand, Xavier Moreau-Gaudry, Guillaume Jean, Denis Fouque
Background: Klotho gene was identified as an aging suppressor. In animals klotho over-expression extends lifespan and defective klotho results in rapid aging and early death. The kidney is the main contributor to circulating klotho levels and during chronic kidney disease, renal klotho gene expression is drastically reduced in animals and humans as well. Objective: We aimed to determine the consequences of a serum klotho defect on cardiovascular morbidity and mortality during chronic dialysis...
April 11, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28396120/klotho-expression-in-osteocytes-regulates-bone-metabolism-and-controls-bone-formation
#11
Hirotaka Komaba, Jovana Kaludjerovic, Dorothy Z Hu, Kenichi Nagano, Katsuhiko Amano, Noriko Ide, Tadatoshi Sato, Michael J Densmore, Jun-Ichi Hanai, Hannes Olauson, Teresita Bellido, Tobias E Larsson, Roland Baron, Beate Lanske
Osteocytes within the mineralized bone matrix control bone remodeling by regulating osteoblast and osteoclast activity. Osteocytes express the aging suppressor Klotho, but the functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression in osteocytes as a potent regulator of bone formation and bone mass. Targeted deletion of Klotho from osteocytes led to a striking increase in bone formation and bone volume coupled with enhanced osteoblast activity, in sharp contrast to what is observed in Klotho hypomorphic (kl/kl) mice...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28387374/klotho-preservation-via-histone-deacetylase-inhibition-attenuates-chronic-kidney-disease-associated-bone-injury-in-mice
#12
Wenjun Lin, Yanning Li, Fang Chen, Shasha Yin, Zhihong Liu, Wangsen Cao
Bone loss and increased fracture are the devastating outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD) resulting from Klotho deficit-related mineral disturbance and hyperparathyroidism. Because Klotho down-regulation after renal injury is presumably affected by aberrant histone deacetylase (HDAC) activities, here we assess whether HDAC inhibition prevents Klotho loss and attenuates the CKD-associated bone complication in a mouse model of CKD-MBD. Mice fed adenine-containing diet developed the expected renal damage, a substantial Klotho loss and the deregulated key factors causally affecting bone remodeling, which were accompanied by a marked reduction of bone mineral density...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28371258/n-3-polyunsaturated-fatty-acids-increase-hepatic-fibroblast-growth-factor-21-sensitivity-via-a-ppar%C3%AE-%C3%AE-klotho-pathway
#13
Wenqi Yang, Xu Chen, Yan Liu, Ming Chen, Xinwei Jiang, Tianran Shen, Qing Li, Yan Yang, Wenhua Ling
SCOPE: Fibroblast growth factor 21 (FGF21) participated in fish oil-mediated hepatic lipid-regulation and anti-inflammatory effects in high-fat diet fed-mice. However, fish oil supplementation did not significantly increase FGF21 protein levels. Whether fish oil-induced benefits in the liver are related to hepatic FGF21 sensitivity remains unclear. METHODS AND RESULTS: Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD) or a fish oil-supplemented high-fat diet (FOD) for 12 weeks...
March 30, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28352317/activation-of-peroxisome-proliferator-activated-receptor-%C3%AE-inhibits-vascular-calcification-by-upregulating-klotho
#14
Lijuan Cheng, Lei Zhang, Jun Yang, Lirong Hao
Cardiovascular diseases are common in patients with chronic kidney disease. One of the key symptoms is the calcification of the vascular smooth muscle cells (VSMCs), which is induced by dysregulated mineral metabolism with high circulating levels of inorganic phosphate (Pi) and calcium. Klotho, which was originally identified as an aging suppressor gene, has been shown to be associated with vascular calcification. Since Klotho was recently identified as a target for nuclear receptor peroxisome proliferator-activated receptor (PPAR) γ, the present study aimed to determine whether PPARγ regulates VSMC calcification through modulating the expression levels of Klotho...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28349330/klotho-regulates-cigarette-smoke-induced-autophagy-implication-in-pathogenesis-of-copd
#15
Lingling Li, Min Zhang, Liqin Zhang, Yusheng Cheng, Xiongwen Tu, Zhiwei Lu
INTRODUCTION: Chronic obstructive pulmonary disease is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway, though its role in human diseases remains unclear. We hypothesized that an anti-aging protein, Klotho plays an important role in regulating autophagy in response to cigarette smoke (CS)...
March 28, 2017: Lung
https://www.readbyqxmd.com/read/28347910/acute-lung-injury-complicating-acute-kidney-injury-a-model-of-endogenous-%C3%AE-klotho-deficiency-and-distant-organ-dysfunction
#16
REVIEW
Connie C W Hsia, Priya Ravikumar, Jianfeng Ye
The lung interfaces with atmospheric oxygen via a large surface area and is perfused by the entire venous return bearing waste products collected from the entire body. It is logical that the lung is endowed with generous anti-oxidative capacity derived both locally and from the circulation. The single-pass pleiotropic alpha-Klotho (αKlotho) protein was discovered when its genetic disruption led to premature multi-organ degeneration and early death. The extracellular domain of αKlotho is cleaved by secretases and released into circulation as endocrine soluble αKlotho protein and exerting wide-ranging cytoprotective effects including anti-oxidation on distant organs especially the lung, which exhibits high sensitivity to circulating αKlotho insufficiency...
March 24, 2017: Bone
https://www.readbyqxmd.com/read/28337713/the-potential-role-of-fibroblast-growth-factor-21-in-lipid-metabolism-and-hypertension
#17
REVIEW
Zhe Huang, Aimin Xu, Bernard M Y Cheung
Fibroblast growth factor (FGF) 21 belongs to the FGF superfamily that is involved in cell proliferation and differentiation, neural development, angiogenesis, and metabolism. FGF21 requires β-Klotho as a co-receptor. Tissues involved in metabolism such as the liver, adipose tissues, skeletal muscle, and pancreas express FGF21. Starvation increases hepatic expression of FGF21, which then acts centrally to increase hepatic gluconeogenesis. FGF21 also increases fatty acid oxidation. This may be relevant in cold exposure, when expression of FGF21 is induced...
April 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/28336912/fgf21-regulates-t-cell-development-in-the-neonatal-and-juvenile-thymus
#18
Yoshiaki Nakayama, Yuki Masuda, Hiroya Ohta, Tomohiro Tanaka, Miwa Washida, Yo-Ichi Nabeshima, Ayumi Miyake, Nobuyuki Itoh, Morichika Konishi
We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in the thymus as well as in the liver. In line with this expression profile, Fgf21 was recently reported to protect against ageing-related thymic senescence by improving the function of thymic epithelial cells (TECs). However, the function of Fgf21 in the juvenile thymus remained to be elucidated. We investigated the physiological roles of Fgf21 in the juvenile thymus and found that young Fgf21 knockout mice, but not β-Klotho knockout mice nor adult Fgf21 knockout mice, showed a significant reduction in the percentage of single-positive CD4(+) and CD8(+) thymocytes without obvious alteration in TECs...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334808/downregulation-of-pathways-implicated-in-liver-inflammation-and-tumorigenesis-of-glycogen-storage-disease-type-ia-mice-receiving-gene-therapy
#19
Goo-Young Kim, Joon Hyun Kwon, Jun-Ho Cho, Lisa Zhang, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is characterized by impaired glucose homeostasis and long-term risks of hepatocellular adenoma (HCA) and carcinoma (HCC). We have shown that the non-tumor-bearing (NT), recombinant adeno-associated virus (rAAV) vector-treated GSD-Ia mice (AAV-NT mice) expressing a wide range (0.9-63%) of normal hepatic glucose-6-phosphatase-α activity maintain glucose homeostasis and display physiologic features mimicking animals living under calorie restriction (CR). We now show that in AAV-NT mice, the signaling pathways of the CR mediators, AMP-activated protein kinase (AMPK) and sirtuin-1 are activated...
March 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28332126/klotho-suppresses-high-phosphate-induced-osteogenic-responses-in-human-aortic-valve-interstitial-cells-through-inhibition-of-sox9
#20
Fei Li, Qingzhou Yao, Lihua Ao, Joseph C Cleveland, Nianguo Dong, David A Fullerton, Xianzhong Meng
Elevated level of blood phosphate (Pi) associated with chronic kidney disease (CKD) is a risk factor of aortic valve calcification. Aortic valve interstitial cells (AVICs) display osteogenic responses to high Pi although the underlying mechanism is incompletely understood. Sox9 is a pro-chondrogenic factor and may play a role in ectopic tissue calcification. Circulating and kidney levels of Klotho are reduced in patients with CKD. We hypothesized that Sox9 mediates high Pi-induced osteogenic responses in human AVICs and that Klotho inhibits the responses...
March 22, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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