Search Results (17)

α-Klotho is an anti-aging protein linked to various age-related diseases. Environmental metal exposure has been associated with oxidative stress and aging, but its effect on α-Klotho levels remains unclear. This study investigated the relationship between urinary metal concentrations and serum α-Klotho levels using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2016 cycles. A total of 4071 adults aged 40 to 79 years were included in the analysis. After adjusting for potential confounders, positive associations were found between serum α-Klotho levels and barium (Ba), cesium (Cs), and molybdenum (Mo), while tungsten (W) and uranium (U) were negatively correlated with α-Klotho levels. The combined effects of multiple metals were further analyzed using the qgcomp model, which demonstrated a negative correlation between increased metal mixtures and serum α-Klotho levels. Specifically, U, total arsenic (t-As), W, cadmium (Cd), antimony (Sb), and lead (Pb) contributed to the reduction of α-Klotho levels, while Ba, Cs, dimethylarsinic acid (DMA), Mo, thallium (Tl), and cobalt (Co) were positively associated with α-Klotho levels. These findings suggest that exposure to certain metals, particularly in combination, may reduce serum α-Klotho levels, potentially accelerating aging processes. Further studies should investigate the underlying mechanisms responsible for these associations. Full article

Background: Our previous research in an experimental model of current environmental human exposure to cadmium (Cd) (female rats fed a diet containing Cd at 1 and 5 mg/kg for up to 2 years) revealed that chronic treatment with this toxic element destroyed the metabolism of the bone tissue, decreased mineralisation, and weakened bone biomechanical properties, whereas the co-administration of a 0.1% chokeberry (Aronia melanocarpa L. (Michx.) Elliott berry) extract (AME) ameliorated the osteotoxic action of Cd. Methods: In this study, it was explored whether the unfavourable effect of Cd and the protective action of AME might be mediated by the impact on the metabolism of bone essential elements such as calcium (Ca) and inorganic phosphorus (P_i), including the pathways of its regulation by calciotropic hormones (parathormone—PTH, calcitonin—CT, and 1,25-dihydroxyvitamin D₃—1,25(OH)₂D₃) and Klotho. Results: Low-level Cd treatment (1 mg/kg) caused only a temporary elevation in the serum PTH concentration and a decline in the concentration of CT. Moderate treatment with Cd (5 mg/kg) destroyed the body homeostasis of both mineral elements (lowered their concentrations in the serum and enhanced urinary loss), influenced the serum concentrations of Klotho and calciotropic hormones, as well as reduced the concentrations of 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase) and 1,25(OH)₂D₃ in the kidney. The application of AME during Cd intoxication improved the pathways involved in maintaining Ca and P_i homeostasis and allowed subjects to maintain the proper levels of these elements in the serum and urine. Conclusions: In conclusion, Cd at low-to-moderate exposure may exert an unfavourable impact on bone by influencing the pathways involved in regulating Ca and P_i metabolism and destroying the body status of these minerals. It seems that the possible mechanism of the osteoprotective effect of AME during chronic intoxication with this toxic element involves normalization of the concentrations of calciotropic hormones and Klotho in the serum and improvement of the homeostasis of Ca and P_i. This study provided further evidence that chokeberry products may be an effective strategy in counteracting the unfavourable effects of chronic low-to-moderate exposure to Cd. Full article

Background/Objectives: Soluble αKlotho (sαKlotho) and fibroblast growth factor 23 (FGF-23) are increased in acute heart failure (AHF). This study aimed to assess changes in serum sαKlotho and FGF-23 concentrations during an episode of AHF as well as the usefulness of both biomarkers for predicting long-term prognosis. Methods: The study included 104 consecutive patients hospitalized in t he intensive cardiac care unit due to AHF (mean age, 65.8 ± 14.6 years; mean ejection fraction, 31.4% ± 14). New-onset AHF was reported in 43.3% of the population. Blood samples were measured at entry and on discharge from hospital. The main clinical outcomes assessed in this study were all-cause mortality or rehospitalization due to HF during a 3-year follow-up. Results: At admission sαKlotho, FGF-23, and NT-pro BNP levels, compared with discharge, were significantly higher at p < 0.001, p < 0.001, and p < 0.001 respectively. The 3-year Kaplan–Meier analysis, based on tertiles, revealed, for sαKlotho levels from Tertile 1 on admission and at discharge, a 2-fold higher rate of all-cause mortality or rehospitalization for HF compared with Tertile 3 (p = 0.006 and p = 0.028, respectively). One-third of patients showed an increase in FGF-23 and sαKlotho levels during hospitalization. Patients with the highest percentage increase in the levels of both biomarkers had an elevated risk of all-cause morality or hospitalization for HF (hazard ratio, 2.75; confidence interval, 1.19–6.35; p = 0.02). Conclusions: sαKlotho and FGF-23 levels are elevated during an episode of AHF. Low sαKlotho levels are associated with an increased risk of all-cause mortality or rehospitalization for HF. Increases in sαKlotho and FGF-23 values during hospitalization identify patients with poor prognosis. Full article

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 (Col4a3^−/−). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency (kl/kl). We found that adenine, Col4a3^−/−, and kl/kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD. Full article

Being involved in various physiological and pathophysiological mechanisms (ageing, kidney damage, cardiovascular diseases, etc.), Klotho is a parameter of increasing interest. Studies in veterinary medicine are still rare, but it is exciting to find out whether the findings obtained can be transferred to animals. The aim of this study was therefore to investigate Klotho in cats. This study addressed α-Klotho concentrations in the serum of two groups of cats: one diseased group affected by hypertrophic cardiomyopathy (n = 27) and one healthy control group (n = 35). α-Klotho concentrations in serum were measured using an ELISA. The results were evaluated in the context of several echocardiographic measurement parameters in the diseased group. No significant difference between α-Klotho concentrations in the two groups was found. A slight negative correlation was found between α-Klotho concentrations and the relation of left atrium/aorta (La/Ao) in the diseased group. Gaining initial information on α-Klotho in cats, it was not possible to draw definite conclusions concerning cardiomyopathies in this species. The assessment of Klotho should be considered in terms of its broad implications in disease processes, but it is also recommended to focus on specific disease features. Both approaches might be promising as possible applications of Klotho in veterinary medicine. Full article

Background: Klotho is widely recognized as a protein that combats aging and possesses antioxidative characteristics, which have been implicated in the pathophysiology of numerous diseases. There is emerging evidence suggesting that the consumption of dietary nutrients, particularly those rich in antioxidants, could be associated with serum Klotho concentrations. Dietary vitamin C is one of the critical nutrients that possesses antioxidant properties. Nonetheless, the association between dietary vitamin C consumption and serum Klotho concentrations remains unclear. Objective: Aiming to evaluate the relationship between serum Klotho concentrations and dietary vitamin C consumption among Americans aged 40 to 79, we conducted a population-based study. Methods: From the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016, a grand total of 11,282 individuals who met the criteria were selected as eligible participants for the study. Serum Klotho concentrations were measured using an ELISA kit that is commercially available. Trained interviewers evaluated the consumption of dietary vitamin C in the diet through a 24-hour dietary recall technique. A generalized linear model was used to evaluate the correlation between the consumption of dietary vitamin C in the diet and serum Klotho concentrations. Further examination was conducted using restricted cubic spline (RCS) analysis to explore the non-linear correlation between dietary vitamin C consumption in the diet and serum Klotho concentrations. Results: After accounting for possible confounding factors, serum Klotho concentrations rose by 1.17% (95% confidence interval (CI): 0.37%, 1.99%) with every standard deviation (SD) rise in dietary vitamin C consumption. With the first quintile of dietary vitamin C consumption as a reference, the percentage change of serum Klotho concentrations in the fifth quintile of dietary vitamin C consumption was 3.66% higher (95% CI: 1.05%, 6.32%). In older, normal-weight, and male participants, the subgroup analysis revealed a stronger correlation between dietary vitamin C consumption and serum Klotho concentrations. Analysis of RCS showed a linear positive association between dietary vitamin C consumption and the levels of serum Klotho concentrations. Conclusion: The findings of this research indicate a strong and positive correlation between dietary vitamin C consumption and serum Klotho concentrations among the general adult population in the United States. Further studies are needed to validate the present findings and to explore specific mechanisms. Full article

Background: The relationship between dietary carbohydrate intake and serum Klotho levels, an aging biomarker, remains uncertain. Objective: This study aimed to investigate the association between dietary carbohydrate intake and serum Klotho levels among American adults aged 40–79. Methods: We analyzed data from 10,669 adults aged 40–79 years who participated in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Trained interviewers assessed dietary carbohydrate intake using a 24 h dietary recall. Serum Klotho concentrations were measured using commercially available ELISA kits provided by IBL International, Japan, which served as the study outcome. Generalized linear models were used to assess the relationship between the carbohydrate energy percentage and serum Klotho concentration, and restricted cubic spline (RCS) analysis was employed to explore any nonlinear associations. Results: After adjusting for multiple variables, we observed a nonlinear inverse J-shaped relationship (p for non-linearity < 0.001) between the carbohydrate energy percentage and serum Klotho levels. Specifically, the highest serum Klotho levels were associated with a total carbohydrate energy percentage ranging from 48.92% to 56.20% (third quartile). When the carbohydrate energy percentage was evaluated in quartiles, serum Klotho levels decreased by 5.37% (95% CI: −7.43%, −3.26%), 2.70% (95% CI: −4.51%, −0.86%), and 2.76% (95% CI: −4.86%, −0.62%) in the first quartile (<41.46%), second quartile (41.46% to 48.92%), and fourth quartile (≥56.20%), respectively, compared to the third quartile. This relationship was more pronounced in male, non-obese and non-diabetic participants under 60 years of age. Conclusion: A non-linear inverse J-shaped relationship exists among the general U.S. middle-aged and older population between the carbohydrate energy percentage and serum Klotho levels, with the highest levels observed at 48.92% to 56.20% carbohydrate intake. Full article

Circulating Klotho levels are significantly reduced in subjects with type 2 diabetes mellitus (T2DM) and in kidney disease patients. In this work, the relationship between Klotho levels and the coronary artery disease (CAD) burden in subjects with T2DM and preserved kidney function was analyzed. For this, we performed a cross-sectional case-control study involving 133 subjects with T2DM and 200 age-, sex- and CAD-incidence-matched, non-diabetic patients undergoing non-emergency diagnostic coronary angiography. All of them were non-albuminuric and with normal glomerular filtration rates. The concentrations of serum Klotho, fibroblast growth factor 23, and inflammatory markers were also measured. As expected, the serum Klotho concentration was lower in the T2DM group (12.3% lower, p = 0.04). However, within the group of patients with T2DM, those subjects with CAD presented significantly higher Klotho levels than those without significant coronary stenosis (314.5 (6.15–562.81) vs. 458.97 (275.2–667.2) pg/mL; p = 0.02). Multiple regression analysis revealed that serum Klotho was positively related with stenosis values exclusively in subjects with T2DM (adjusted R2 = 0.153, p < 0.01). Moreover, logistic regression analysis showed that Klotho was positively associated with the presence of significant CAD in the group of T2DM patients (OR: 1.001; p = 0.041). Our data suggest that higher levels of circulating Klotho in subjects with T2DM and preserved kidney function are associated with the presence of significant CAD. Full article

The causes and mechanisms underlying adolescent idiopathic scoliosis (AIS) remain unclear, and the available information regarding metabolic imbalances in AIS is still insufficient. This investigation aimed to evaluate the concentrations of specific bone remodeling-related agents in postmenarcheal girls diagnosed with AIS. The study encompassed thirty-six scoliosis patients and eighteen age-matched healthy individuals assigned to the control group. The patients underwent clinical and radiological examinations to assess the degree of the spinal deformity, type of curvature, and skeletal maturity. Blood and urine samples were collected from all participants and serological markers were measured using an enzyme-linked immunosorbent assay. Our study results demonstrated that the balance of phosphate–calcium and parathormone levels seems normal in individuals with AIS. Furthermore, no statistically significant differences were observed in the content of Klotho protein, osteocalcin, osteoprotegerin, C-terminal telopeptide of type I collagen (CTX), sclerostin, and alkaline phosphatase. Nevertheless, the serum levels of vitamin D (25-OH-D) were lowered, while N-terminal propeptide of type I procollagen (PINP), and fibroblast growth factor-23 (FGF23) were increased in the AIS group, with p-values of 0.044, 0.001, and 0.022, respectively. This finding indicates the potential involvement of these factors in the progression of AIS, which necessitates further studies to uncover the fundamental mechanisms underlying idiopathic scoliosis. Full article

Klotho is a beta-glucuronidase that reveals both anti-inflammatory and anti-oxidative properties that have been associated with mechanisms of aging. The study aimed to analyze the relationships between the serum concentration of soluble α-Klotho and cellular activity of two populations of lymphocytes; T and NKT-like cells corresponding to the level of cytokine secretion; i.e., IFN-γ, TNF-α, and IL-6. The studied population comprised three age groups: young individuals (‘young’), seniors aged under 85 (‘old’), and seniors aged over 85 (‘oldest’). Both NKT-like and T cells were either non-cultured or cultured for 48 h and stimulated appropriately with IL-2, LPS or PMA with ionomycin to compare with unstimulated control cells. In all studied age groups non-cultured or cultured NKT-like cells revealed higher expressions of TNF-α, IL-6, and IFN-γ than T cells. α-Klotho concentration in serum decreased significantly in the process of aging. Intriguingly, only IFN-γ expression revealed a positive correlation with α-Klotho protein serum concentration in both non-cultured and cultured T and NKT-like cells. Since IFN-γ is engaged in the maintenance of immune homeostasis, the observed relationships may indicate the involvement of α-Klotho and cellular IFN-γ expression in the network of adaptive mechanisms developed during the process of human aging. Full article

Klotho is an anti-aging gene. Studies have revealed its association with insulin resistance. Visceral fat is related to insulin resistance, and the sagittal abdominal diameter (SAD) can serve as a biomarker for visceral fat (VF). This study investigated the association between SAD and serum Klotho concentration (SKC). We enrolled 2301 participants from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) dataset, and 49.2% of the enrolled individuals were male. Qualified participants were separated into four quartiles according to the SAD value. SKC values were obtained by ELISA. Demographic characteristics, body mass index (BMI), systolic blood pressure, and biochemistry parameters with significance were analyzed using multivariate linear regression models. The mean age of the study participants was 57.22 ± 10.53 years. The fully adjusted regression model showed a negative association between SAD and SKC (p < 0.05), with a β-coefficient of −12.02. We also analyzed subgroups of participants according to age and BMI. Participants with an age ≥65 and <65 years old were each negatively associated with SKC, and this association was significant for participants with a BMI ≥ 30 kg/m² (p = 0.001, β-coefficient: −18.83). We also found a concentration-dependent relationship between SAD and SKC. In conclusion, VF and SKC are associated, and SAD can serve as a surrogate of VF and an indicator of SKC. Full article

Anemia is a complication of chronic kidney disease (CKD). Phosphate and fibroblast growth factor-23 (FGF23) have a close relationship, as both are related to the pathogenesis of anemia. However, the possible interplay between them regarding their effect on anemia has not been evaluated. This was a cross-sectional study of 896 participants from the NEFRONA study (273 CKD3, 246 CKD4-5, 282 dialysis and 95 controls). The levels of 25(OH) and 1,25(OH)₂ vitamin D, intact FGF23 (iFGF23) and soluble Klotho were measured, together with standard blood biochemistries. Anemia was defined as hemoglobin levels < 13 g/dL in men and <12 g/dL in women. Patients with anemia (407, 45.4%) were younger, mostly men and diabetic; were in advanced CKD stages; had lower calcium, 1,25(OH)₂ vitamin D and albumin levels; and had higher ferritin, phosphate, intact PTH, and iFGF23. An inverse correlation was observed between hemoglobin and both iFGF23 and phosphate. The multivariate logistic regression analyses showed that the adjusted risk of anemia was independently associated with higher serum phosphate and LogiFGF23 levels (ORs (95% CIs) of 4.33 (2.11–8.90) and 8.75 (3.17–24.2), respectively (p < 0.001)). A significant interaction between phosphate and iFGF23 (OR of 0.66 (0.53–0.83), p < 0.001) showed that the rise in the adjusted predicted risk of anemia with the increase in iFGF23 was steeper when phosphate levels were low. Phosphate levels acted as modifiers of the effect of iFGF23 concentration on anemia. Thus, the effect of the increase in iFGF23 levels was stronger when phosphate levels were low. Full article

It has been hypothesized that α-Klotho deficiency might contribute to chronic inflammation in patients with end-stage renal disease (ESRD), especially those on hemodialysis (HD). Serum Klotho levels by some authors are considered a potential predictor of cerebrovascular events. Therefore, we analyzed serum levels of α-Klotho with ELISA and inflammation-related cytokines in HD patients. Sixty-seven HD patients and 19 healthy people were recruited between November 2017 and June 2021. A Cytometric Bead Array (CBA) was used to determine the level of different cytokines: IL-12p70, TNF, IL-10, IL-6, IL-1β, and IL-8. A human Klotho ELISA kit was used to determine the level of α-Klotho in the plasma samples of HD patients. There was no difference in serum levels of α-Klotho between HD patients and healthy people. Patients had increased serum IL-6 and IL-8. Significant positive correlations existed between the concentration of α-Klotho and the serum concentrations of IL-12p70, IL-10, and IL-1β. However, in a multivariable linear regression analysis, only patients’ age was associated independently with α-Klotho level. Serum α-Klotho was not associated with higher mortality risk in HD patients. While these results draw attention to potential relationships between α-Klotho proteins and inflammatory markers in HD patients, our cross-sectional study could not confirm the pathogenic link between α-Klotho, inflammation, and cardiovascular mortality. Full article

The purpose of this study was to assess the clinical usefulness of assaying the fibroblast growth factor (FGF-23), Klotho, osteocalcin, N-terminal telopeptide of type I collagen (NTX), and sclerostin levels in patients with primary hyperparathyroidism (PHPT) as markers of bone damage as well as for surgical treatment success. Seventeen patients with hypercalcemic PHPT and normal kidney function were studied. In all patients, PTH (parathormone), serum calcium, and creatinine were performed before and six months after parathyroidectomy (PTX). The studied group included patients whose PTH and calcium concentrations normalized post-operatively and with confirmed histopathological diagnosis. The control group consisted of nine age-matched healthy volunteers. The PHPT patients had elevated concentrations of FGF-23, osteocalcin, and NTX and reduced levels of sclerostin, as compared to the control group. After PTX, osteocalcin, NTX, and sclerostin levels normalized. The plasma values of FGF-23 decreased significantly, but remained higher than in healthy subjects. Serum Klotho protein levels did not differ significantly in the two groups. These results suggest that osteocalcin and NTX may potentially be considered as markers of PHPT progression. Additionally, serum normalization of osteocalcin, NTX, and sclerostin might be considered as indicators of PTX success. On the other hand, FGF-23 can represent a parameter reflecting the degree of calcium–phosphate imbalance in PHPT patients, but its usefulness in monitoring the effects of PTX requires further research. The clinical utility of assaying Klotho in PHPT remains to be confirmed. Full article

Hyperphosphatemia is commonly present in end-stage renal disease. Klotho (KL) is implicated in phosphate homeostasis since it acts as obligate co-receptor for the fibroblast growth factor 23 (FGF23), a major phosphaturic hormone. We hypothesized that genetic variation in the KL gene might be associated with alterations in phosphate homeostasis resulting in hyperphosphatemia. We performed sequencing for determining KL gene variants in a group of resistant hyperphosphatemic dialysis patients. In a 67-year-old female, blood DNA sequencing revealed a heterozygous deletion of a T at position 1041 (c.1041delT) in exon 2. This variation caused a frameshift with substitution of isoleucine for phenylalanine and introduction of a premature termination codon (p.Ile348Phefs*28). cDNA sequencing showed absence of deletion-carrier transcripts in peripheral blood mononuclear cells suggesting degradation of these through a nonsense-mediated RNA decay pathway. Experiments in vitro showed that p.Ile348Phefs*28 variant impaired FGF23 signaling pathway, indicating a functional inactivation of the gene. In the patient, serum levels of KL were 2.9-fold lower than the mean level of a group of matched dialysis subjects, suggesting a compromise in the circulating protein concentration due to haploinsufficiency. These findings provide a new loss-of-function variant in the human KL gene, suggesting that genetic determinants might be associated to clinical resistant hyperphosphatemia. Full article