Serum α-Klotho Levels Research Articles

Association between plasma trans fatty acids and serum α-klotho levels in adults in the United States of America: an analysis of the NHANES 2009–2010 datasets

BackgroundThis study aimed to explore the potential associations between trans fatty acid (TFA) and α-klotho levels.MethodsDatasets from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) were analysed for this study. Multivariable linear regression and restricted cubic spline (RCS) analyses were performed to examine the relationships between plasma TFA and serum α-klotho levels.ResultsA total of 1,205 participants were included, with a geometric mean (GM) of 803.60 (95% CI: 787.45, 820.00) pg/mL for serum α-klotho levels. RCS analysis revealed L-shaped relationships between TFA and α-klotho levels. The inflection points for palmitelaidic acid (PA), vaccinic acid (VA), elaidic acid (EA), and total TFA levels were 4.55, 20.50, 18.70, and 46.40 µmol/L, respectively. Before reaching the inflection point, serum α-klotho levels were negatively correlated with plasma PA, VA, EA and total TFA levels, with β values (95% CI) of -0.15 (-0.24, -0.06), -0.16 (-0.23, -0.09), -0.14 (-0.22, -0.05) and − 0.19 (-0.27, -0.11), respectively. Linolelaidic acid (LA) levels exhibited an inverse and linear association with α-klotho levels ( Pnonlinearity=0.167, Poverall<0.001). L-shaped relationships between TFA and α-klotho levels were also observed in the subgroups of participants who were aged < 65 years, were male, did not exercise, were ex-smokers, and were overweight/obese.ConclusionsL-shaped correlations between plasma PA, VA, EA, and total TFA levels and serum α-klotho levels were observed among adults in the United States.

The association between exposure to volatile organic chemicals and serum α-Klotho in USA middle to old aged population: A cross-sectional study from NHANES 2011–2016

BackgroundVolatile Organic Compounds (VOCs) constitute an omnipresent category of environmental contaminants. Numerous studies have identified associations between various VOCs and human diseases. The anti-aging protein α-Klotho has been shown to exert protective influences across a variety of disease origins and progressions. This study aims to explore the relationship between serum α-Klotho levels and exposure to VOCs in humans. MethodsThis analysis utilized data from 1672 participants aged from 40 to 79 years in 2011–2016 NHANES. Exposure to VOCs was assessed through measurements of urinary VOC metabolites (mVOCs), with 16 mVOCs selected for analysis. Multivariate generalized linear models (GLM), restricted cubic splines (RCS), weighted quantile sum (WQS) regression models, and Bayesian kernel machine regression (BKMR) models were employed to examine the connection between serum α-Klotho and individual mVOCs and mVOCs mixtures, as well as to identify the primary monomeric mVOCs responsible for these associations. ResultsOur research revealed that 8 mVOCs exhibited inverse associations with serum α-Klotho levels in GLM and RCS models. Particularly noteworthy, N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), a metabolite of acrylonitrile, emerged as the most influential mVOC in both WQS and BKMR models. Furthermore, the mVOCs mixture was found to be negatively correlated with serum α-Klotho. The detrimental effects of mVOCs on serum α-Klotho were observed to significantly diminish in individuals with elevated serum vitamin D levels. ConclusionOur study highlights a significant inverse relationship between serum α-Klotho and the mixture of mVOCs, indicating that exposure to VOCs may impact the molecular pathways of aging and related diseases by influencing α-Klotho concentrations. Remarkably, the attenuation of this association by high serum vitamin D levels implies potential therapeutic strategies. Our study underscores the importance of minimizing VOCs exposure to mitigate the adverse effects on α-Klotho. Further research is warranted to elucidate the underlying mechanisms of these relationships.

Association Between the Serum α-Klotho Level and Insulin Resistance in Adults: NHANES 2007–2016

ABSTRACT Objective This study aimed to investigate the relationship between serum α-Klotho levels and insulin resistance (IR), a precursor to type 2 diabetes. Methods The study analyzed data from 4,758 adult participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. The relationship between α-Klotho concentration and IR was assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and odds ratios (OR) derived from logistic regression models. Results Results showed that every 1-ln increase in α-Klotho concentration raised the HOMA-IR value by 0.55 (95% confidence interval 0.35–0.74) and the odds of IR by 64% (odds ratio 1.64; 95% confidence interval 1.28–2.1). The odds of IR was 40% greater in highest tertile than in the lowest tertile. Conclusion The findings of this study underscore a significant correlation between increased serum α-Klotho levels and the prevalence of IR.

The prognostic value of serum α-klotho in age-related diseases among the US population: A prospective population-based cohort study

Objectiveα-Klotho is a potential biological marker of aging with satisfactory clinical applicability. However, its prognostic significance in age-related diseases has largely been undermined. Therefore, we aimed to report the prognostic value of serum α-klotho levels in age-related diseases. MethodsParticipants with available serum α-klotho data from the National Health and Nutrition Examination Survey (2007–2016) were included. Their survival status was collected at 7.62 ± 2.99 years after serum α-klotho data was collected, and the endpoint was all-cause and cardiovascular mortality. A Cox regression model was established to examine the association between serum α-klotho levels and all-cause and cardiovascular mortality. ResultsThe present study included 13,746 U.S. adults with a survey-weighted mean age of 56.19 ± 10.42 years old. Of these, 52.2 % were female and 72.9 % were non-Hispanic whites. The optimal cutoff value of serum α-klotho for predicting all-cause mortality risk in the general population was 603.5 pg/ml. Individuals with low serum α-klotho (<603.5 pg/ml) had a significantly higher risk of all-cause (adjusted HR: 1.34(1.18–1.52), P < 0.001) and cardiovascular mortality (adjusted HR: 1.63(1.27–2.10), P < 0.001). Subgroup analysis showed that low serum α-klotho level was an independent risk factor for all-cause and cardiovascular mortality in people with hypertension, congestive heart failure, diabetes mellitus, and emphysema, while it was an independent risk factor for all-cause mortality in patients with renal insufficiency. ConclusionA low serum α-klotho concentration (<603.5 pg/ml) could serve as a marker of all-cause and cardiovascular mortality in the general population and in people with age-related diseases, including hypertension, congestive heart failure, diabetes mellitus, and emphysema.

Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association

BackgroundFrailty, a clinical syndrome intricately linked with the aging process, stands as a harbinger of numerous adverse outcomes, most notably mortality. This study aimed to elucidate the association between serum α-klotho concentration and mortality patterns, including all-cause and cause-specific mortality, in patients with frailty.MethodsThe study employed Cox proportional hazard models, smoothed curve fitting, and supplementary analyses, encompassing threshold effect analysis, subgroup and sensitivity analyses, to explore the relationship between α-klotho levels and mortality, including all-cause, CVD, and cancer-related mortality.ResultsAmong the 2,608 frail individuals (mean age: 60.78 [SD 10.48] years; 59.89% female), the mortality stood at 25.35% during a median follow-up period of 6.95 years. Both unadjusted and adjusted models revealed a significant inverse association between higher serum α-klotho levels and the risk of all-cause and CVD-related mortality ([mean(95% CI) 0.68 (0.55, 0.83)] for all-cause mortality; [mean(95% CI) 0.48 (0.32, 0.74)] for CVD-related mortality, all P for trend < 0.001). Notably, log2–klotho displayed a U-shaped correlation with all-cause mortality and cancer mortality, characterized by thresholds of 9.48 and 9.55, respectively. The robustness of these findings was consistently supported by subgroup and sensitivity analyses.ConclusionThis study unveils a U shaped association between serum α-klotho levels and both all-cause and cancer-related mortality among middle-aged and elderly individuals with frailty in the United States. The identified serum α-klotho thresholds, at 714.8 pg/ml for all-cause mortality and 750.6 pg/ml for cancer-related mortality, hold promise as potential targets for interventions aimed at mitigating the risks of premature death and cancer within this vulnerable population.

Association between serum α-Klotho levels and osteoarthritis prevalence among middle-aged and older adults: an analysis of the NHANES 2007–2016

BackgroundAs individuals age, the prevalence of osteoarthritis tends to increase gradually. α-Klotho is a hormone renowned for its anti-aging properties. However, the precise role of serum α-Klotho in osteoarthritis is still not fully comprehended. MethodsWe conducted a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. Serum α-Klotho levels were measured using an enzyme-linked immunosorbent assay (ELISA). Osteoarthritis was assessed through self-reported questionnaires. Through univariate and multivariate logistic regression analyses, smooth curve fitting, threshold effect analysis, and subgroup analyses, we delved into the potential association between them. ResultsThe study encompassed a cohort of 10,265 participants. In fully adjusted models of multivariate logistic regression analysis, we identified a negative correlation between serum ln α-Klotho and OA (OR = 0.77, 95% CI: 0.65−0.91, p = 0.003). When stratifying serum α-Klotho levels into tertiles, individuals in the highest tertile exhibited a 26% reduced risk of OA compared to those in the lowest tertile (OR = 0.84, 95% CI: 0.73−0.97, p = 0.014). Subsequent analyses indicated a linearly negative association. In subgroup analyses, we explored the relationship between serum ln α-Klotho and osteoarthritis across diverse populations, revealing the persistence of this association in the majority of subgroups. ConclusionSerum α-Klotho levels exhibit a significant negative linear correlation with the prevalence of osteoarthritis in middle-aged and elderly populations in the United States.

Association between smoking, smoking cessation and serum α-klotho levels among American adults: National Health and Nutrition Examination Survey.

α-klotho is an anti-aging protein. The correlation between smoking, smoking cessation and serum α-klotho levels remains controversial. The aim of this study was to investigate the association between smoking, smoking cessation and serum α-klotho levels. This cross-sectional study finally included 4877 participants, aged 40-79 years, who participated in the National Health and Nutrition Examination Survey studies from 2013 to 2016. Of these, 2312 (47.4%) were men and 894 (18.3%) were current smokers, and the mean age of the participants was 57.8±10.7 years. Multivariate linear regression modeling was used to assess the association between smoking, smoking cessation and serum α-klotho levels. After adjustment for multiple confounders, this study observed that smoking was negatively associated with serum α-klotho levels (β: -58.3; 95% confidence interval CI: -82.0 to -34.6; p<0.001), whereas smoking cessation was positively associated with serum α-klotho levels (β: 52.3; 95% CI: 24.1 to 80.6; p<0.001). In subgroup and interaction analyses, p-value for the interaction between smoking and race on serum klotho levels was found to be less than 0.001. The correlation between smoking, smoking cessation and serum α-klotho levels remained stable after propensity score matching (β: -54.1; 95% CI: -81.5 to -26.7; p<0.001, β: 54.8; 95% CI: 24.2 to 85.4; p<0.001). In a large sample population, the present study found that smoking, smoking cessation and serum α-klotho levels were associated in opposite directions.

U-SHAPED ASSOCIATION OF Α-KLOTHO WITH ALL AND CAUSE-SPECIFIC MORTALITY IN US ADULTS: A SECOND ANALYSIS OF NHANES

Abstract Laboratory studies have shown that mice deficient in the klotho gene have a shortened lifespan, but the epidemiological evidence linking circulating α-klotho to mortality is inconsistent. Our aim was to clarify the association between serum α-klotho and mortality using a representative population. From the National Health and Nutrition Examination Survey (2007-2016), 13748 participants aged 40-79 years with serum α-klotho test data were selected and followed up to 31 December 2019. Participants were equally divided into 5 groups (Q1 &amp;lt; 622.8pg/ml, Q2: 622.8-739.1pg/ml, Q3: 739.1-857.7pg/ml, Q4: 857.7-1033.1pg/ml, Q5 &amp;gt;1033.1pg/ml) based on quantiles of serum α-klotho concentrations, with the Q3 serving as the reference group. Multivariate Cox proportional hazards regression analysis showed that both participants with low and high serum α-klotho levels had a higher risk of all-cause mortality, compared to the reference group (HR[95%CI], Q1:1.38[1.13,1.69], Q5:HR 1.23[1.02,1.47]). We further found a non-linear and U-shaped association between α-klotho and all-cause, cancer-cause, and diabetes-cause mortality, but an L-shaped association between α-klotho and CVD-cause mortality by using cubic spline function model and smooth curve fitting (penalized spline method). We observed a significant negative association between α-klotho (log-transformed) and all-cause mortality (HR[95%CI], 0.70[0.55,0.91]) in the subgroup of participants with normal liver function. In conclusion, the U-shaped association was found between serum α-klotho and all-cause mortality among US adults, and the reasons for the increased risk of death associated with high levels of α-klotho require further investigation.

Association between cigarette smoking and serum alpha klotho levels among US adults over 40-years-old: a cross-sectional study

Alpha klotho (α-Klotho) is an anti-aging molecule associated with aging and several diseases. Previous studies have reported inconsistent levels of α-Klotho in smokers. This study aimed to demonstrate serum α-Klotho levels in smokers among the US population. This cross-sectional study recruited 11,559 participants (aged 40–79 years; 48.2% males). All data were collected from the 2007–2016 National Health and Nutrition Examination Survey. The study comprised adults with reliable Klotho and smoking questionnaire results. The relationship between smoking and serum α-klotho levels was assessed using multivariate linear regression models after adjusting for potential confounders. We also performed a stratified analysis of clinically important variables. The mean serum α-klotho level among the 11,559 participants was 843.85 pg/mL. After full adjustment, habitual smoking was significantly associated with decreased serum levels of α-klotho level (β = − 34.89; 95% CI − 54.97, − 14.81; P = 0.0013) in the total study population. Furthermore, the stratified analysis indicated that the association was insignificant in the 60–79 age group. Quitting smoking was not significantly associated with serum levels of α-klotho as expected (P = 0.1148) in the total study population. However, stratified analyses showed a significant inversed association in the male, those with chronic kidney disease, or those with cancer who quit smoking (all P < 0.05). Cigarette smoking was inversely associated with serum α-Klotho levels among US adults.

Correlation between serum α-Klotho levels and different stages of periodontitis

BackgroundPeriodontitis is an inflammatory disease characterized by inflammation and progressive destruction of periodontal tissues including alveolar bone. α-klotho protein is a multifunctional protein related to age-related diseases, inflammatory diseases, and bone metabolism-related diseases. However, large-sample epidemiological research evidence on the correlation between α-Klotho and the aggravation of periodontitis stages is still lacking.MethodsCross-sectional study data of participants aged between 40 and 79 years in the National Health and Nutrition Examination Survey 2013‒2014 were selected and analyzed. The stages of periodontitis of the participants were determined according to the 2018 World Workshop Classification of Periodontal and Peri-implant Diseases. The serum α-Klotho levels in people with periodontitis in different stages were evaluated. Then the correlation between serum α-Klotho levels and different stages of periodontitis was analyzed by multiple linear regression (stepwise regression method).ResultsA total of 2378 participants were included in the study. The serum α-Klotho levels in people with stage I/II, III and IV periodontitis were 896.16 ± 304.84, 871.08 ± 266.42 and 840.52 ± 286.24 pg/mL, respectively. The levels of α-Klotho in people with stage IV periodontitis were significantly lower than those in people with stage I/II and III periodontitis. Linear regression analysis results showed that compared to stage I/II periodontitis, serum α-Klotho levels were significantly negatively correlated with stage III (B ± SE = -37.28 ± 16.00, 95% CI: -68.66 ~ -25.91, P = 0.020) and stage IV (B ± SE = -69.37 ± 16.11, 95% CI: -100.97 ~ -37.77, P < 0.001) periodontitis.ConclusionThe serum α-Klotho levels were negatively correlated with the severity of periodontitis. With the aggravation of periodontitis stages, the serum α-Klotho levels gradually decreased.

Sex differences in the association between serum α-Klotho and depression in middle-aged and elderly individuals: A cross-sectional study from NHANES 2007–2016

BackgroundKlotho is a well-known anti-aging protein that exerts pleiotropic effects; however, little is known regarding serum α-Klotho in the context of depression. Here, we evaluated the association between serum α-Klotho levels and depression in middle-aged and older individuals. MethodsIn this cross-sectional study, data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016 with a total of 5272 participants who were ≥40 years of age. Depression was evaluated using the 9-item Patient Health Questionnaire (PHQ-9). The association between serum α-Klotho levels and depression was determined on the basis of multivariable logistic regression models. ResultsThe mean age of the enrolled adults was 58.94 ± 10.54 years, of which 49.5 % were female. When serum α-Klotho was log10-transformed, it was significantly inversely associated with depression in females in the final adjusted model (odds ratio [OR], 0.32; 95 % confidence interval [CI], 0.12–0.85). In the contrast, serum α-Klotho (log10) was significantly positively associated with depression in males in one of the adjusted models (OR, 3.71; 95 % CI, 1.17–11.8), and this disappeared after adjusting other covariates (all P > 0.05). Based on further stratified respective analyses of females and males, the results were stable. LimitationsThe cross-sectional study could not yield any conclusions regarding causality. ConclusionsIn the present study, serum α-Klotho levels were negatively related to the prevalence of depression in middle-aged and elderly women. This study provides new evidence of sex differences in the association between serum α-Klotho levels and depression.

Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants.

Exposure to perfluoroalkyl and polyfluoroalkyl substances causes oxidative stress, which is strongly associated with adverse health effects. Klotho protein plays an anti-aging role via antioxidation activity. We investigated the levels of serum α-Klotho and PFAS exposure in adults who participated in the National Health and Nutrition Examination Survey from 2013 to 2016. A nationally representative subsample of 1,499 adults aged 40-79 years was analyzed for the associations of serum α-Klotho levels with serum PFAS exposures by correlation analysis and multiple general linear models. Of note, the potential confounding factors including age and gender were adjusted. Quantile-based g-computation models were used to assess the effects of mixed PFAS exposure on serum α-Klotho levels. The weighted geometric mean of serum α-Klotho was 791.38 pg/mL for the subjects during 2013-2016. After adjusting for potential confounders, serum Klotho levels showed a statistically significant downward trend with increasing quartiles of PFOA and PFNA. Multivariate adjusted general linear regression analysis showed that increased exposure to PFNA was substantially associated with lower serum levels of α-Klotho, and each 1-unit increase in PFNA concentration was accompanied by a 20.23 pg/mL decrease in α-Klotho level; while no significant association was observed between other PFAS exposures and serum α-Klotho levels. It was negatively correlated between α-Klotho and Q4 for PFNA relative to the lowest quartile (Q1) of exposure (P = 0.025). It was found that the strongest negative correlation between PFNA exposure and serum α-Klotho levels was in the middle-aged (40-59 years) female participants. Furthermore, the mixture of the four PFAS substances showed an overall inverse association with serum α-Klotho concentrations, with PFNA being the major contributor. Taken together, in a representative sample of the U.S. middle-aged and elderly populations, serum concentrations of PFAS, especially PFNA, have been negatively associated with serum levels of α-Klotho, which is strongly associated with cognition and aging. It was important to note that the majority of associations were limited to middle-aged women. It will be meaningful to clarify the causal relationship and the pathogenic mechanisms of PFAS exposure and α-Klotho levels, which is helpful to aging and aging-related diseases.

Association between Serum α-Klotho Levels and Behçet Disease.

Endothelial dysfunction (ED) has a well-known role in promoting vascular inflammation in Behçet disease (BD). α-klotho is involved in regulation of endothelial function, and its reduction has been reported to be associated with ED. To assess serum α-klotho in patients with BD, compared with healthy control individuals. In a cross-sectional study, 55 patients with BD and 30 age- and sex-matched healthy controls were enrolled, and their serum levels of α-klotho were measured. Common clinical symptoms in patients with BD were oral aphthous ulcers, uveitis, and genital ulcers. Median (IQR) serum α-klotho levels in the BD and control groups were 0.30 (0.20-0.70) and 1.00 (0.70-2.52) ng/mL, respectively. The difference was statistically significant (P = .005). No significant correlation was observed between serum α-klotho and age (r = 0.194; P = .14). Serum α-klotho levels in patients with uveitis were significantly lower. α-klotho may have a role in the pathogenesis of ED and is a potential biomarker for uveitis in BD.

Fibroblast growth factor 23-Klotho and mineral metabolism in the first year after pediatric kidney transplantation: A single-center prospective study.

The role of fibroblast growth factor 23 (FGF23) levels in mineral metabolism before and after kidney transplantation in pediatric patients is poorly understood. We prospectively evaluated 24 patients under 18 years of age (4.5 [3.3-9.8]years) who underwent living kidney transplantation between July 2016 and March 2018, and measured intact FGF23 and serum αKlotho levels, and other parameters of mineral metabolism before and after transplantation (Day 7, 1 and 4 months, and 1 year). Relationships between parameters were examined by linear analysis. FGF23 level was 440.8 [63.4-5916.3]pg/ml pre-transplant and decreased significantly to 37.1 [16.0-71.5]pg/ml at Day 7 post-transplant (-91.6%, p < .001). Thereafter, it remained at normal levels until 1 year. αKlotho level was 785 [568-1292]pg/ml pre-transplant and remained low at Day 7 and 1 month post-transplant, with an increasing trend at 4 months. Post-transplant phosphorus levels were significantly decreased compared with pre-transplant, with a lowest level of 1.7 [1.3-2.9]mg/dl, -5.7 [-6.8, -3.8] SD at Day 4, followed by gradual recovery. Phosphorus levels and the ratio of tubular maximum phosphate reabsorption were significantly and negatively associated with pre-transplant FGF23 until 4 months of post-transplant. Pre-transplant αKlotho was negatively associated with pre-transplant FGF23 but not FGF23 or other parameters after transplantation. FGF23 in pediatric kidney transplant patients decreased rapidly after transplantation and associated with post-transplant hypophosphatemia and increased phosphorus excretion. Post-transplant αKlotho was low early post-transplant but tended to increase subsequently. Post-transplant αKlotho was unaffected by pre-transplant FGF23 or other factors, suggesting pre-transplant chronic kidney disease status has no effect.

Exposure to p-dichlorobenzene and serum α-Klotho levels among US participants in their middle and late adulthood

P-dichlorobenzene (p-DCB) is a volatile compound commonly used as pest repellent and air deodorant in the home and public buildings, leading to a widespread exposure in indoor environments. There has been an increasing concern about its metabolic and endocrine effects. In this study, we explored the relation between p-DCB exposure and serum levels of soluble α-Klotho, an anti-aging hormone, in US adults. A nationally representative subsample of 1485 adults 40–79 ages in the 2013–2016 National Health and Nutrition Examination Survey was analyzed for the association between p-DCB exposure, measured as urinary concentrations of 2,5-dichlorophenol (2,5-DCP), the major metabolite of p-DCB, and serum α-Klotho levels using multiple general linear models, adjusting for potential confounders. Age- and sex-specific analyses were further conducted. The weighted geometric mean of urinary 2,5-DCP was 2.43 μg/L and the weighted mean of serum α-Klotho was 831.97 pg/mL in the study participants during 2013–2016. After adjusting for potential confounders and urinary creatinine, urinary 2,5-DCP was significantly associated with decreased serum levels of α-Klotho (regression coefficient β = −9.88; p = 0.0133) in the total study population. When age- and sex-specific analyses being conducted, a significantly inverse association was found in older adults aged 60–79 years (β = −20.40; p = 0.0001) and in males (β = −13.81; p = 0.0097), but not in the middle ages (40–59 years) and in females. The strongest association was observed in older (60–79 years) male participants, with a 25.43 pg/mL reduction of α-Klotho levels per 1-unit increase of 2,5-DCP concentrations (p = 0.0008). This is the first study demonstrating a relation between p-DCB exposure, measured as 2,5-DCP, and decreased α-Klotho levels in older males. Additional studies would further explore these interactions and elucidate the pathogenesis of the potential effects of p-DCB exposure on aging.

Para-dichlorobenzene exposure and serum α-Klotho levels among US participants in their middle and late adulthood

Para-dichlorobenzene exposure and serum α-Klotho levels among US participants in their middle and late adulthood

Association between environmental exposure to perchlorate, nitrate, and thiocyanate and serum α-Klotho levels among adults from the National Health and nutrition examination survey (2007–2014)

Background & aimsAging is a pathophysiological process driven by a diverse set of complex biological processes, and environmental pollution plays an important role in this process. This study aimed to explore the association between serum α-Klotho levels and urinary perchlorate, nitrate, and thiocyanate levels.MethodsThis secondary dataset analysis included 4875 participants (mean age, 57.69 year; male, 49.58%; non-Hispanic White, 47.67%) from the US National Health and Nutrition Examination Survey (2007–2014). Enzyme-linked immunosorbent assay was used to quantify α-Klotho levels, and ion chromatography coupled with electrospray tandem mass spectrometry was used to quantify thiocyanate, nitrate, and perchlorate levels. Multivariate linear regression models were applied to estimate the association between perchlorate, nitrate, and thiocyanate levels and serum α-Klotho levels.ResultsUrinary thiocyanate levels were negatively associated with α-Klotho levels (β = − 0.006; 95% confidence interval, − 0.010 to − 0.003; P = 0.0004) after adjusting for age, sex, body mass index, race, alcohol consumption, estimated glomerular filtration rate, underlying disease, physical activity, smoking status, usual energy intake, and urinary creatinine and serum cotinine levels and mutual adjustment of urinary perchlorate, urinary nitrate, and urinary thiocyanate levels. The α-Klotho level in participants in the highest quartile was higher by 50.567 ng/mL (β = 50.567; 95% confidence interval, 14.407 to 86.726; P = 0.009) than that in participants in the lowest quartile of urinary perchlorate. A linear relationship was observed between urinary thiocyanate and α-Klotho levels.ConclusionsUrinary thiocyanate levels were negatively associated with serum α-Klotho levels. Urinary thiocyanate should be further investigated as a potential mediator of aging and age-related diseases.

Association of α-klotho and lead and cadmium: A cross-sectional study

Epigenetic aging is associated with harmful health effects such as oxidative stress from heavy metal exposure. We considered the relationship between genes and heavy metals in association with oxidative stress and then investigated the association between serum α- klotho and lead and cadmium exposure among adults in the United States from 2007 to 2016 participating in the National Health and Nutrition Examination Survey (NHANES). Samples included 9800 adults aged 40 to 79 years with measurements of serum α-klotho, lead and cadmium, and complete covariate data. Lead and cadmium levels were measured by inductively coupled plasma mass spectrometry and serum α-klotho levels were measured using enzyme-linked immunosorbent assay (ELISA). Multivariate linear regression analysis was used to estimate the association between serum α-klotho and blood lead, blood cadmium, and urinary cadmium. A percent increase in blood lead, blood cadmium, and urinary cadmium was associated with a statistically significant 4.0 % (p < 0.001), 2.0 %, (p = 0.003) and 1.0 % (p = 0.020) decrease in serum klotho. After adjustment, a percent increase in blood lead was associated with a statistically significant 4.0 % (p < 0.001) decrease in serum klotho; blood and urinary cadmium did not show any statistically significant associations after adjustment (β (95 % CI), p-value for blood cadmium: 0.00 (−0.02–0.01), p = 0.573; urinary cadmium: −0.01 (−0.03–0.01), p = 0.210). Mean serum klotho levels showed a statistically significant decreasing trend with increasing blood lead quartiles (unadjusted and all-adjusted geometric means and 95 % confidence intervals of serum klotho (in pg/mL) for Q1, Q2, Q3, and Q4: unadjusted: 827.49 (814.20–840.92), 811.92 (794.73–829.48), 791.48 (775.11–808.19), and 772.01 (754.23–790.29); adjusted: 830.64 (805.53–856.45), 816.07 (789.18–843.87), 800.71 (773.71–828.57), and 784.31 (757.94–811.59)). Blood lead and levels were negatively associated with serum α-klotho levels in a representative population of US adults. These results suggest that blood lead levels may be associated with the serum levels of a protein associated with cognition and aging. Further research is recommended to investigate the causality behind such relationship.

Serum α-Klotho Protein Can Be an Independent Predictive Marker of Oxidative Stress (OS) and Declining Glomerular Function Rate in Chronic Kidney Disease (CKD) Patients.

IntroductionChronic kidney disease (CKD) has been recognized as a global health problem. Progression of CKD to advanced stages is associated with a significant increase in the generation of reactive oxygen species (ROS). An antiaging protein, α-Klotho, is found expressed in the distal convoluted tubules of the kidney where, predominantly, it works to increase calcium absorption and potassium excretion in distal tubule via N-linked glycans. The association of serum α-Klotho with oxidative stress, inflammation, and fibrosis, as seen in CKD, highlights its importance for studying disease prognosis with declining glomerular function rate (GFR).Material and methodsThis was a case-control study consisting of 90 subjects. Fifty diagnosed cases of CKD attending the department of nephrology, SCB Medical College, Cuttack, Odisha, were included, and 40 age and sex-matched healthy volunteers were taken as control. Serum α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. Oxidative stress by estimating the total oxidant load by ferrous oxidation-xylenol orange version 2 (FOX2) method and the total antioxidant capacity of serum by the ferric reducing ability of plasma (FRAP) method. Estimation of the estimated glomerular filtration rate (eGFR) was done using the Cockcroft and Gault equation.ResultsSerum α-Klotho (ng/ml) was found to be 2.59±0.98 in cases as compared to 0.24±0.09 in controls (p< 0.01). The serum total oxidant load (ng/ml) was 1.96±1.01 and 0.05±0.02 in cases and controls, respectively. Serum total antioxidant capacity (µM) was measured as 281.80±78.0 in cases and 862.82±51.86 in controls. (p< 0.01). Serum Klotho has a negative correlation with eGFR in CKD patients (r = -0.065; p = 0.648).ConclusionThe serum α-Klotho level was significantly higher in CKD patients than in healthy volunteers. Both serum α-Klotho and oxidative stress were negatively correlated with eGFR in CKD patients. Serum α-Klotho can be a suitable biomarker in CKD patients with declining GFR.

Association between serum alpha-Klotho and severe abdominal aortic calcification among civilians in the United States

Background and aimsAbdominal aortic calcification (AAC) has been recognized as an independent predictor of cardiovascular disease (CVD) incidence and mortality. The aim of this cross-sectional study is to investigate the relationship between serum α-Klotho, an anti-aging hormone, and severe AAC in United States (US) civilians, which was not documented before. Methods and resultsThe data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES), which included 2267 individuals aged 40–79 years. Serum α-Klotho concentration, categorized into four quartiles, was examined by enzyme linked immunosorbent assay (ELISA). AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. The association between serum α-Klotho and severe AAC was determined by multivariable logistic regression models. After adjusting for multiple covariates, the odds ratios (OR) (95% CI) of severe AAC for participants in serum α-Klotho quartiles 2–4 were 0.83 (0.52, 1.32), 0.56 (0.34, 0.94), and 0.54 (0.32, 0.92), respectively, compared with those in quartile 1 (P for trend = 0.007). The association between serum α-Klotho and severe AAC was stable in the different subgroups (all P for interaction＞0.05). ConclusionIn a sample of US adults, serum α-Klotho levels were negatively related to the risk of severe AAC. Our findings indicated that serum α-Klotho may become a promising tool to predict the incidence and prognosis of CVD.