Downregulation of Klotho expression by dehydration

2011 ◽  
Vol 301 (4) ◽  
pp. F745-F750 ◽  
Author(s):  
Cai Tang ◽  
Ganesh Pathare ◽  
Diana Michael ◽  
Abul Fajol ◽  
Melanie Eichenmüller ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Accelerated Aging ◽  
Early Death ◽  
Renal Tissue ◽  
Hek293 Cells ◽  
Protein Abundance ◽  
Transcript Levels ◽  
Age Related ◽  
Klotho Protein ◽  
Growth Deficit

Klotho, a transmembrane protein, protease, and hormone mainly expressed in renal tissue counteracts aging. Overexpression of Klotho substantially prolongs the life span. Klotho deficiency leads to excessive formation of 1,25(OH)2D3, growth deficit, accelerated aging, and early death. Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. The present study explored the possibility that dehydration influences Klotho expression. Klotho transcript levels were determined by RT-PCR, and Klotho protein abundance was detected by Western blotting in renal tissue from hydrated and 36-h-dehydrated mice as well as in human embryonic kidney (HEK293) cells. Dehydration was followed by a significant decline of renal Klotho transcript levels and protein abundance, accompanied by an increase in plasma osmolarity as well as plasma ADH, aldosterone, and 1,25(OH)2D3 levels. Antidiuretic hormone (ADH; 50 nM) and aldosterone (1 μM) significantly decreased Klotho transcription and protein expression in HEK293 cells. In conclusion, the present observations disclose a powerful effect of dehydration on Klotho expression, an effect at least partially mediated by enhanced release of ADH and aldosterone.

scholarly journals Identifying Significant Biological Markers in Klotho Gene Variants Across Wide Ranging Taxonomy

2015 ◽  
Vol 5 (1) ◽  
pp. 11
Author(s):  
Tommy Rodriguez
Keyword(s):  
Transmembrane Protein ◽  
Genetic Regulation ◽  
Comparative Sequence Analysis ◽  
Biological Aging ◽  
Altered State ◽  
Telomere Attrition ◽  
Related Disease ◽  
Age Related ◽  
Evolutionary Context ◽  
Klotho Protein

<p class="1Body">Biological aging is marked by progressively degenerative physiological change that causes damage to tissues and organs. Errors in biopolymers accumulate over time; mitochondrial dysfunction, telomere attrition, and wider genomic instability lead to an altered state of intercellular communication. In this investigation, my focus will be aimed at examining and identifying specifically critical biomarkers in genetic variants of KLOTHO (a transmembrane protein involved in the genetic regulation of age-related disease) among organisms with varied life spans that range across wide taxonomical rankings. Here, I investigate the correlation between lower and higher frequency a-amino acid compositions in Klotho protein factors within a grouped methodology; as to also include several demonstrative techniques in comparative sequence analysis for inferring relatedness in evolutionary context.</p>

scholarly journals Implication of ferroptosis in aging

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maryam Mazhar ◽  
Ahmad Ud Din ◽  
Hamid Ali ◽  
Guoqiang Yang ◽  
Wei Ren ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurological Disorders ◽  
Accelerated Aging ◽  
Underlying Mechanism ◽  
Toxic Chemicals ◽  
Whole Body ◽  
Regulated Cell Death ◽  
Age Related ◽  
The Subject ◽  
Conventional Cell

AbstractLife is indeed continuously going through the irreversible and inevitable process of aging. The rate of aging process depends on various factors and varies individually. These factors include various environmental stimuli including exposure to toxic chemicals, psychological stress whereas suffering with various illnesses specially the chronic diseases serve as endogenous triggers. The basic underlying mechanism for all kinds of stresses is now known to be manifested as production of excessive ROS, exhaustion of ROS neutralizing antioxidant enzymes and proteins leading to imbalance in oxidation and antioxidant processes with subsequent oxidative stress induced inflammation affecting the cells, tissues, organs and the whole body. All these factors lead to conventional cell death either through necrosis, apoptosis, or autophagy. Currently, a newly identified mechanism of iron dependent regulated cell death called ferroptosis, is of special interest for its implication in pathogenesis of various diseases such as cardiovascular disease, neurological disorders, cancers, and various other age-related disorders (ARD). In ferroptosis, the cell death occur neither by conventional apoptosis, necrosis nor by autophagy, rather dysregulated iron in the cell mediates excessive lipid peroxidation of accumulated lethal lipids. It is not surprising to assume its role in aging as previous research have identified some solid cues on the subject. In this review, we will highlight the factual evidences to support the possible role and implication of ferroptosis in aging in order to declare the need to identify and explore the interventions to prevent excessive ferroptosis leading to accelerated aging and associated liabilities of aging.

scholarly journals Effect of MgCl2 and GdCl3 on ORAI1 Expression and Store-Operated Ca2+ Entry in Megakaryocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3292
Author(s):  
Kuo Zhou ◽  
Xuexue Zhu ◽  
Ke Ma ◽  
Jibin Liu ◽  
Bernd Nürnberg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Kidney Disease ◽  
Protein Abundance ◽  
Rt Pcr ◽  
Calcium Sensing Receptor ◽  
Transcript Levels ◽  
Calcium Sensing ◽  
Store Depletion

In chronic kidney disease, hyperphosphatemia upregulates the Ca2+ channel ORAI and its activating Ca2+ sensor STIM in megakaryocytes and platelets. ORAI1 and STIM1 accomplish store-operated Ca2+ entry (SOCE) and play a key role in platelet activation. Signaling linking phosphate to upregulation of ORAI1 and STIM1 includes transcription factor NFAT5 and serum and glucocorticoid-inducible kinase SGK1. In vascular smooth muscle cells, the effect of hyperphosphatemia on ORAI1/STIM1 expression and SOCE is suppressed by Mg2+ and the calcium-sensing receptor (CaSR) agonist Gd3+. The present study explored whether sustained exposure to Mg2+ or Gd3+ interferes with the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. To this end, human megakaryocytic Meg-01 cells were treated with 2 mM ß-glycerophosphate for 24 h in the absence and presence of either 1.5 mM MgCl2 or 50 µM GdCl3. Transcript levels were estimated utilizing q-RT-PCR, protein abundance by Western blotting, cytosolic Ca2+ concentration ([Ca2+]i) by Fura-2 fluorescence and SOCE from the increase in [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 µM). As a result, Mg2+ and Gd3+ upregulated CaSR and blunted or virtually abolished the phosphate-induced upregulation of NFAT5, SGK1, ORAI1,2,3, STIM1,2 and SOCE in megakaryocytes. In conclusion, Mg2+ and the CaSR agonist Gd3+ interfere with phosphate-induced dysregulation of [Ca2+]i in megakaryocytes.

scholarly journals Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth

BMC Nutrition ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sofia Villagomez ◽  
Dena B. Dubal ◽  
Jessica Hawkins ◽  
Dan Wang ◽  
Janet M. Wojcicki
Keyword(s):  
San Francisco ◽  
Low Income ◽  
Accelerated Aging ◽  
Positive Association ◽  
Dietary Factors ◽  
Sugar Sweetened Beverage ◽  
Protein Levels ◽  
Sweetened Beverages ◽  
Klotho Protein

Abstract Background Klotho is an anti-aging protein mainly expressed in the kidneys with a smaller amount expressed in adipose tissue. Klotho effects include roles in reducing oxidative stress, insulin signaling, adipogenesis and glucose metabolism. Few studies have investigated the role of dietary factors such as sugar sweetened beverages (SSBs) on serum α-klotho levels in young children. Methods Data was collected from 60 low-income Latina pregnant women and their infants in San Francisco from birth until 2 years of life and examined for associations between dietary factors and child secreted α-klotho protein levels at 2 years. Results Mean α-klotho levels were 1782.96 ± 874.56 pg/mL at 2 years of age. Any consumption of SSBs was independently associated with increased α-klotho levels (Beta = 682.79, 95%CI 67.50, 1298.09; p = 0.03). Household income ranging from $25,000 to $50,000 was also correlated to higher levels of α-klotho in children compared with lower income levels (<$25,000) (Beta = 1613.35, 95%CI 527.37, 2699.33; p = 0.005). Conclusions The positive association between SSB intake and α-klotho levels at 2 years may reflect higher phosphate levels consistent with SSB intake. Higher socioeconomic status may be a proxy for reduced stress exposure in children, also associated with higher α-klotho levels. Future studies should evaluate the early impact of exposures to SSBs, stress and accelerated aging in children.

scholarly journals Accelerated aging in normal breast tissue of women with breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shoghag Panjarian ◽  
Jozef Madzo ◽  
Kelsey Keith ◽  
Carolyn M. Slater ◽  
Carmen Sapienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Anomaly Detection ◽  
Breast Tissue ◽  
Preventive Intervention ◽  
Normal Breast Tissue ◽  
Accelerated Aging ◽  
Normal Breast ◽  
Age Related ◽  
Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

scholarly journals NAD+Metabolism in Aging and Cancer

2019 ◽  
Vol 3 (1) ◽  
pp. 105-130 ◽  
Author(s):  
Tyler G. Demarest ◽  
Mansi Babbar ◽  
Mustafa N. Okur ◽  
Xiuli Dan ◽  
Deborah L. Croteau ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Accelerated Aging ◽  
Cancer Therapies ◽  
Nad Metabolism ◽  
Cellular Processes ◽  
Cancer Pathogenesis ◽  
Nicotinamide Mononucleotide ◽  
Age Related

Aging is a major risk factor for many types of cancer, and the molecular mechanisms implicated in aging, progeria syndromes, and cancer pathogenesis display considerable similarities. Maintaining redox homeostasis, efficient signal transduction, and mitochondrial metabolism is essential for genome integrity and for preventing progression to cellular senescence or tumorigenesis. NAD+is a central signaling molecule involved in these and other cellular processes implicated in age-related diseases and cancer. Growing evidence implicates NAD+decline as a major feature of accelerated aging progeria syndromes and normal aging. Administration of NAD+precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) offer promising therapeutic strategies to improve health, progeria comorbidities, and cancer therapies. This review summarizes insights from the study of aging and progeria syndromes and discusses the implications and therapeutic potential of the underlying molecular mechanisms involved in aging and how they may contribute to tumorigenesis.

scholarly journals Human Interferon Inducible Transmembrane Protein 3 (IFITM3) Inhibits Influenza Virus A Replication and Inflammation by Interacting with ABHD16A

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Liang Chen ◽  
Limei Zhu ◽  
Jun Chen
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Transmembrane Protein ◽  
Influenza Viruses ◽  
Expression Level ◽  
Hek293 Cells ◽  
Human Interferon ◽  
Control Group ◽  
Mrna Levels ◽  
Membrane Area

Studies have shown that human interferon inducible transmembrane protein (hIFITMs) family proteins have broad-spectrum antiviral capabilities. Preliminary studies in our laboratory have tentatively proved that hIFITMs have the effect of inhibiting influenza viruses. In order to further study its mechanism and role in the occurrence and development of influenza A, relevant studies have been carried out. Fluorescence quantitative polymerase chain reaction (PCR) detection technology was used to observe the effect of hIFITM3 on the replication of influenza A virus (IVA) and the interaction with hABHD16A. In HEK293 cells, overexpression of hIFITM3 protein significantly inhibited the replication of IVA at 24 h, 48 h, and 72 h; yeast two-hybrid experiment proved that hIFITM3 interacts with hABHD16A; laser confocal microscopy observations showed that hIFITM3 and hABHD16A colocalized in the cell membrane area; the expression level of inflammation-related factors in cells overexpressing hIFITM3 or hABHD16A was detected by fluorescence quantitative PCR, and the results showed that the mRNA levels of interleukin- (IL-) 1β, IL-6, IL-10, tumor necrosis factor- (TNF-) α, and cyclooxygenase 2 (COX2) were significantly increased. But when hIFITM3/hABHD16A was coexpressed, the mRNA expression levels of these cytokines were significantly reduced except COX2. When influenza virus infected cells coexpressing hIFITM3/hABHD16A, the expression level of inflammatory factors decreased compared with the control group, indicating that hIFITM3 can play an important role in regulating inflammation balance. This study confirmed that hIFITM3 has an effect of inhibiting IVA replication. Furthermore, it was found that hIFITM3 interacts with hABHD16A, following which it can better inhibit the replication of influenza virus and the inflammatory response caused by the disease process.

scholarly journals Age-related decrements in cycling and running performance

2004 ◽  
Vol 16 (2) ◽  
pp. 8 ◽  
Author(s):  
A St Clair Gibson ◽  
Ni Lambert ◽  
TD Noakes
Keyword(s):  
Athletic Performance ◽  
Sports Medicine ◽  
Weight Bearing ◽  
Accelerated Aging ◽  
Age Related ◽  
Endurance Cycling ◽  
Order Polynomial ◽  
Bearing Stress ◽  
Rate Of Decline ◽  
The Relationship

Objective. This study examined age-related decrements in athletic performance during running and cycling activities. Design. The age group winning times for males aged between 18 and 70 years competing in the 1999 Argus cycle tour (103 km) and 1999 Comrades running marathon (90 km), South Africa's premier endurance cycling and running events respectively, were examined. Main outcome measures. The relationship between speed (cycling and running respectively) and age was calculated using a 4th order polynomial function. The derivative of each of these functions was determined and then the slope of the function corresponding to each age was calculated. Results. The rate of decline in running speed occurred at an earlier age (~ 32 years) during the running race compared with the cycling tour (~ 55 years). Conclusions. These findings establish a trend that there is ‘accelerated' aging during running which can perhaps be attributed to the increased weight-bearing stress on the muscles during running compared with cycling. SA Sports Medicine Vol.16(2) 2004: 8-11

scholarly journals FRAILTY AND CONSTELLATIONS OF FACTORS IN AGING HIV-INFECTED AND UNINFECTED WOMEN - THE WOMEN’S INTERAGENCY HIV STUDY

2016 ◽  
pp. 1-6
Author(s):  
D.R. GUSTAFSON ◽  
Q. SHI ◽  
M. THURN ◽  
S. HOLMAN ◽  
H. MINKOFF ◽  
...  
Keyword(s):  
At Risk ◽  
Hiv Infection ◽  
Frailty Index ◽  
Accelerated Aging ◽  
Early Death ◽  
Infection Prevalence ◽  
Middle Aged ◽  
Cross Sectional ◽  
Moderate Drinking ◽  
Hiv Women

Background: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. Objectives: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. Design: Cross-sectional. Setting: The Women’s Interagency HIV Study (WIHS). Participants: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-).Measurements: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. Results: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. Conclusions: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger ‘at risk’ populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

Melatonin Prevents the Development of Age-Related Pathology in Male Rats during Accelerated Aging Caused by Impaired Photoperiodism

2021 ◽  
Vol 11 (1) ◽  
pp. 77-82
Author(s):  
I. A. Vinogradova ◽  
Yu. P. Matveeva ◽  
O. V. Zhukova ◽  
V. D. Yunash ◽  
V. N. Anisimov
Keyword(s):  
Accelerated Aging ◽  
Male Rats ◽  
Age Related
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