Serum Klotho Concentration Research Articles

Exploring the Link between Serum Klotho and High-Frequency Hearing Loss in Older Adults.

Klotho is a protein with various biological functions, including anti-aging effects. Although research suggests Klotho plays a key role in auditory function, the relationship between serum Klotho levels and high-frequency hearing loss (HFHL) in older adults remains unclear. We analyzed data from individuals aged 70-79 years participating in the 2009-2010 cycle of the National Health and Nutrition Examination Survey. Multivariate logistic regression models were employed to assess the relationship between serum Klotho levels and HFHL. Restricted cubic splines were utilized to evaluate linearity and examine the dose-response relationship. Additionally, we performed subgroup analyses to evaluate the consistency of this relationship across various subgroups. In this study of 422 elderly individuals aged 70-79 years (mean age 73.8 years, with 47.4% male participants), the median serum Klotho concentration was 754.6 pg/mL. Multivariable logistic regression analysis consistently demonstrated that higher serum Klotho levels were associated with a reduced risk of HFHL across various models (ORs: 0.24-0.32, p = 0.020-0.028). Additionally, restricted cubic spline analysis confirmed a linear negative association between serum Klotho levels and HFHL risk, with a p-value for nonlinearity of 0.474. Subgroup analyses did not reveal any statistically significant interactions modifying this relationship. Serum Klotho levels are inversely associated with the risk of HFHL. 3 Laryngoscope, 2024 Laryngoscope, 2024.

Gender differences in the relationship between the triglyceride-glucose index and serum Klotho concentrations among the middle-aged and elderly: a cross-sectional analysis

BackgroundThe triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored.MethodsA cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point.ResultsA total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (β = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009).ConclusionsThe findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants.

Inverse association of the systemic immune-inflammation index with serum anti-ageing protein Klotho levels in individuals with osteoarthritis: A cross-sectional study.

The association between the systemic immune-inflammation index (SII) and the serum soluble-Klotho concentration (pg/ml) in osteoarthritis (OA) patients is unknown. This study aimed to investigate the relationship between the SII and serum soluble-Klotho levels in OA patients. All study data were obtained from the National Health and Nutrition Examination Survey (NHANES) database (n = 1852 OA patients; age range = 40-79 years). The SII and serum Klotho measurement data are from the NHANES mobile examination centre. The SII values were divided into quartiles (Q1-4: 0.02-3.36, 3.36-4.78, 4.79-6.70, and 6.70-41.75). A multivariate linear regression model was constructed to evaluate the association between the SII and serum Klotho levels in OA patients; interaction tests were conducted to test the stability of the statistical results. Multivariate linear regression revealed a negative linear relationship between the SII and serum Klotho concentration in OA patients (β = -6.05; 95% CI: -9.72, -2.39). Compared to Q1, Q4 was associated with lower serum Klotho concentrations (β = -59.93; 95% CI: -96.57, -23.28). Compared with that of Q1, the β value of Q2-Q4 showed a downwards trend as the SII increased (Ptrend <0.001). The stratified analysis results indicated that the SII had a greater sensitivity in predicting serum Klotho concentrations in OA patients aged 60-79 years (Pinteraction = 0.028). There was a significant negative linear correlation between the SII and serum Klotho concentration in OA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in OA patients. Klotho may be a potential anti-inflammatory drug for OA treatment.

Serum Klotho and insulin resistance: Insights from a cross-sectional analysis.

The prevalence of diabetes has surged globally, posing significant health and economic burdens. Insulin resistance underlies the initiation and development of type 2 diabetes. Klotho is a crucial endogenous antiaging factor, associated with atherosclerotic cardiovascular diseases, cancer, neurological disorders, and renal diseases. It additionally has a function in controlling glucose metabolism and holds promise as a new therapeutic target for diabetes. However, its relationship with insulin resistance remains unclear. This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2007 to 2016 data to investigate the relationship between serum Klotho concentrations and insulin resistance. In this observational study, information from the NHANES spanning 2007 to 2016 was employed. The sample consisted of 6371 participants. Weighted linear regression model and chi-square tests were utilized to assess differences in continuous and categorical variables, respectively, among groups categorized by Klotho quartiles. The relationship between Klotho and HOMA-IR (homeostatic model assessment of insulin resistance) was studied using multiple linear regression. Smooth curve fitting was used to analyze nonlinear relationships and the inflection point was determined through a 2-stage linear regression method. After adjusting for multiple confounding factors, serum Klotho levels were found to be positively correlated with insulin resistance [0.90 (0.68, 1.13)]. This correlation is nonlinear and exhibits a saturation effect, with the inflection point identified at 1.24 pg/µL. When Klotho levels are below 1.24 pg/µL, for every unit increase in Klotho, HOMA-IR increases by 1.30 units. Conversely, when Klotho levels exceed 1.24 pg/µL, there is no correlation between HOMA-IR and Klotho. Subgroup analysis reveals that the relationship between HOMA-IR and Klotho varies depending on diabetes and body mass index (BMI). This positive correlation was most prominent in the obese nondiabetic population. There is a positive correlation between serum Klotho and insulin resistance.

Revisiting the mechanisms linking blood glucose to cognitive impairment: new evidence for the potential important role of klotho.

The association between blood glucose and cognition is controversial. Klotho is an anti-aging protein with neural protective effects. This study aimed to use a population-based study to disentangle the relationship between blood glucose levels and cognitive function in older adults, and to explore the role of klotho in it. A total of 1445 eligible participants from National Health and Nutrition Examination Survey (NHANES) 2011-2014 were included in our study. Cognitive function was assessed by Digit Symbol Substitution Test (DSST) and categorized into four quartiles (Q1-Q4). General characteristics and laboratory test results including serum klotho concentration and blood glucose levels were collected. Associations of cognitive function and klotho levels with blood glucose concentrations were explored through multivariate linear regression models. Mediation models were constructed to figure out the mediating role of klotho. All three multivariate linear regression models showed a negative correlation between blood glucose and cognitive function. (Model 1, β=-0.149, 95%CI: -0.202,-0.096, p=0.001; Model 2, β=-0.116, 95%CI: -0.167,-0.065, p=0.001; Model 3, β=-0.007, 95%CI: -0.118,-0.023, p=0.003). Mediation analysis showed that klotho mediated the statistical association between blood glucose level and cognitive function with proportions (%) of 12.5. Higher blood glucose levels are associated with poorer cognitive performance in non-diabetic older adults, partially mediated through lower klotho levels.

Association Between Serum Klotho and Chronic Obstructive Pulmonary Disease in US Middle-Aged and Older Individuals: A Cross-Sectional Study from NHANES 2013-2016.

This study sought to examine the potential association between serum Klotho levels and the prevalence of COPD in the United States. This study was a cross-sectional analysis involving 4361 adults aged 40-79 years participating in the US National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Our investigation utilized multivariate logistic regression and restricted cubic spline (RCS) regression to explore the potential correlation between serum Klotho concentrations and the prevalence of COPD. Additionally, we conducted stratified and interaction analyses to evaluate the consistency and potential modifiers of this relationship. In this study encompassing 4631 patients (with an average age of 57.6 years, 47.5% of whom were male), 445 individuals (10.2%) were identified as having COPD. In the fully adjusted model, ln-transformed serum Klotho was negatively associated with COPD (OR = 0.71; 95% CI: 0.51-0.99; p = 0.043). Meanwhile, compared with quartile 1, serum Klotho levels in quartiles 2-4 yielded odds ratios (ORs) (95% CI) for COPD were 0.84 (0.63~1.11), 0.76 (0.56~1.02), 0.84 (0.62~1.13), respectively. A negative relationship was observed between the ln-transformed serum Klotho and occurrence of COPD (nonlinear: p = 0.140). the association between ln-transformed serum Klotho and COPD were stable in stratified analyses. Serum Klotho was negatively associated with the incidence of COPD, when ln-transformed Klotho concentration increased by 1 unit, the risk of COPD was 29% lower.

Interplay of Systemic Immune-Inflammation Index and Serum Klotho Levels: Unveiling a New Dimension in Rheumatoid Arthritis Pathology.

Aim: The association between the systemic immune-inflammation index (SII) and serum Klotho concentrations (pg/ml) in patients with rheumatoid arthritis (RA) has not been elucidated. The purpose of this study was to clarify the relationship between the SII and serum Klotho concentrations in RA patients. Methods: All data come from the National Health and Nutrition Examination Survey (NHANES) database in the United States, which included 982 RA patients (age range: 40 to 79 years). The measurement data of the SII and serum Klotho are all from the NHANES mobile examination centre. We constructed a multivariate linear regression model to evaluate the association between the SII and serum Klotho levels in RA patients and conducted a subgroup analysis to test the stability of the statistical results. Results: Multivariate linear regression results indicated a negative linear relationship between the SII and serum Klotho concentrations in RA patients (β = -6.33, 95% CI [confidence interval]: -10.15 to -2.53). Compared to the quartile 1 group, the quartile 4 group was associated with significantly lower (P<0.001) serum Klotho concentrations (β = -120.93, 95% CI: -174.84 to -67.02). Compared with the quartile 1 group, with the increase in the SII, the β value showed a decreasing trend (P trend < 0.001). The subgroup analysis showed that none of the covariates affected the stability of these results (all P for interaction ≥ 0.05). Conclusion: There is a significant negative linear association between the SII and serum Klotho concentrations in RA patients. The SII can serve as a predictive indicator of serum Klotho concentrations in RA patients, and Klotho may be a potential anti-inflammatory target for RA treatment.

Klotho protein concentrations as a function of sex, APOE, family history or Alzheimer’s disease biomarker status in an at‐risk cohort

AbstractBackgroundThe KLOTHO gene encodes for a longevity and neuroprotective klotho hormone. The non‐human animal literature suggests that higher levels of klotho promote resilience against Alzheimer’s disease (AD)‐related neuropathology. Human carriers of the functionally advantageous KLOTHO KL‐VS variant have higher serum klotho levels and show attenuation of proteins involved in AD‐related neuropathology (β‐amyloid (Aβ) and tau). How klotho protein relates to AD neuropathology or risk factors (APOE gene, family history, sex) is less well understood.MethodThe sample consists of 318 middle‐aged and older, cognitively normal adults (MeanAge(SD) = 63.8(6.66); range = 44‐80; 65% female) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Research Center studies. Stratifications of the sample into positive vs. negative AD biomarker status were made using local reference cutpoints measured via cerebrospinal fluid (CSF: Aβ40, Aβ42, total tau, phosphorylated tau, and their respective ratios to Aβ42) or positron emission tomography (PET; β‐amyloid: 11C‐Pittsburgh compound B(PiB); tau: 18F‐MK‐6240). We examined whether baseline serum klotho protein concentrations differed based on AD biomarker status (whether positive (i.e., abnormal) for β‐amyloid or tau) or characteristics related to AD risk.ResultThere were no significant differences in baseline serum klotho concentrations between those considered positive vs. negative for β‐amyloid or tau whether by CSF or PET (P’s&gt;0.19). Females (844 pg/mL) compared to males (765 pg/mL) had significantly higher serum klotho concentrations (F (1,317) = 7.37; P = 0.007). No differences were observed based on APOE4 status or parental AD history (P’s&gt;0.31).ConclusionWe confirm sex‐dependent difference in serum klotho favoring females. No significant differences in serum klotho protein concentrations were observed based on APOE4, AD family history or AD biomarker status (+/‐) in our cohort of middle‐aged and older, cognitively normal adults, albeit enriched for AD risk. While this may seem in contrast to a recent case‐control study (Grøntvedt, 2022) suggesting that klotho protein is associated with β‐amyloid and tau burden and clinical stages of AD, that study measured circulating klotho in plasma and included participants with MCI and AD diagnoses. Our results add to the growing KLOTHO literature and highlight the need for better understanding of the underlying mechanisms for its effects.

Association of Dietary Vitamin C Consumption with Serum Klotho Concentrations.

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. 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. 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. 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. 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.

Association between serum Klotho concentration and hyperlipidemia in adults: a cross-sectional study from NHANES 2007-2016.

The Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults. The study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships. In our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86-0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58-0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects. This study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.

Relationship of Klotho with cognition and dementia: Results from the NHANES 2011–2014 and Mendelian randomization study

The relationships of Klotho levels with cognition and dementia are poorly understood. This study aimed to investigate the association between Klotho levels and cognitive function and to determine causality between Klotho and dementia using Mendelian randomization (MR). Based on data from the National Health and Nutrition Survey (NHANES) 2011–2014, this study consisted of 1875 older adults aged 60–79 years. Cognitive function was assessed by the digit symbol substitution test (DSST). We performed weighted multivariable-adjusted linear regression to assess the association between Klotho concentrations and cognitive function. Then, 2-sample MR was conducted to assess the causal relationship between Klotho and dementia. The inverse variance weighted (IVW) method was used as the primary analysis. We observed a positive association between serum Klotho concentrations and the results of the Digit Symbol Substitution test (DSST) (T2: β 2.16, 95% CI: 0.30–4.01, P = 0.03, T3: β 2.48, 95% CI: 0.38–4.57, P = 0.02) after adjusting for the covariates. Moreover, there was also a potential nonlinear relationship between Klotho and DSST. The IVW method showed that genetically predicted high Klotho levels were not significantly associate with any type of dementia, including Alzheimer’s disease (OR = 1.03, 95% CI: 0.96–1.10, P = 0.46), vascular dementia (OR = 1.04, 95% CI: 0.87–1.25, P = 0.66), frontotemporal dementia (OR = 0.73, 95% CI: 0.47–1.14, P = 0.16), or dementia with Lewy bodies (OR = 1.03, 95% CI: 0.87–1.23, P = 0.73). In the cross-sectional observational study, Klotho and cognitive function were significantly correlated; however, findings from MR studies did not indicate a causal relationship between Klotho and dementia.

The significance of serum Klotho to hearing loss: a potential protector under noise pollution.

The issue of hearing protection in the presence of noise pollution is of great importance in the fields of environmental science and clinical medicine. Currently, the clinical significance of Klotho in relation to hearing has not been revealed. The aim of this study was to examine the correlation between serum Klotho levels and Pure Tone Average (PTA) hearing thresholds among individuals in the U.S.. The analysis involved a sample of 1,781 individuals aged 20 to 69, obtained from the 2007-2012 National Health and Nutrition Examination Survey. Various methods were utilized for the analysis, including univariate and multivariate linear regression, stratified analysis, smooth curve fitting, a two-segment linear regression model, and log-likelihood ratio analysis. The results of the univariate analysis indicated that serum Klotho concentration, age, education level, hypertension, diabetes, and smoking all exhibited a significant influence on PTAs. After adjusting for potential confounding factors, it was observed that a decrease in serum Klotho was significantly associated with PTA thresholds at low frequency (β = -0.002; 95% CI: -0.003, -0.001; P = 0.004), speech frequency (β = -0.002; 95% CI: -0.003, -0.001; P = 0.007), and high frequency (β = -0.002; 95% CI: -0.003, -0.001; P = 0.045). Specifically, for every 1pg/ml decrease in serum Klotho concentration, the PTAs increased by 0.002dB. Moreover, age and gender-specific analyses revealed significant associations. For individuals aged 59-69, a significant association was found between serum Klotho concentration and high-frequency PTA (β = -4.153; 95% CI: -7.948, -0.358; P = 0.032). Additionally, among females, significant associations were observed between serum Klotho concentration and speech-frequency PTA (β = -1.648, 95% CI: -3.197, -0.099; P = 0.037) as well as high-frequency PTA (β = -3.046; 95% CI: -5.319, -0.772; P = 0.009). Finally, the results of smooth curve fitting and threshold effect analyses indicated a potential negative linear correlation between serum Klotho concentration and PTA thresholds. In conclusion, a lower level of serum Klotho was found to be associated with increased hearing thresholds, particularly among the elderly population. This finding has significant implications for the prevention and treatment of hearing damage.

Inverse J-Shaped Relationship of Dietary Carbohydrate Intake with Serum Klotho in NHANES 2007-2016.

The relationship between dietary carbohydrate intake and serum Klotho levels, an aging biomarker, remains uncertain. This study aimed to investigate the association between dietary carbohydrate intake and serum Klotho levels among American adults aged 40-79. 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. 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. 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.

Association of Klotho with Coronary Artery Disease in Subjects with Type 2 Diabetes Mellitus and Preserved Kidney Function: A Case-Control Study.

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.

The association of serum Klotho concentrations with hyperlipidemia prevalence and lipid levels among US adults: a cross-sectional study

BackgroundKlotho has anti-oxidative and anti-inflammatory properties. However, little is known about whether high Klotho concentrations were associated with reduced hyperlipidemia risk and improved plasma lipid levels.MethodsParticipants with complete data on serum Klotho and plasma lipid concentrations from the 2007–2016 National Health and Nutrition Examination Survey were included. Weighted regression models were fitted to explore the association of Klotho concentrations with hyperlipidemia risk and plasma lipid levels while restricted cubic spline models were applied to explore the dose–response relationship. Additionally, we assessed the mediating effects of C-reaction protein (CRP) on the foregoing association.ResultsIndividuals in the fourth and fifth quintile of serum Klotho had an adjusted odds ratio (OR) of 0.77 (95%CI: 0.65, 0.93) and 0.67 (95%CI: 0.65, 0.93) for hyperlipidemia. Doubling of serum Klotho concentrations was associated with decreased hyperlipidemia risk (OR = 0.81; 95%CI: 0.68, 0.95) and triglyceride levels (13.25 mg/dL; 95%CI: 4.02, 22.47), with a monotonic dose–response relationship. Individuals in the fourth and fifth quintile of serum Klotho had a 0.07 (95%CI: 0.002, 0.13), 0.08 (95%CI: 0.02, 0.15) and 0.05 (95%CI: –0.03, 0.12) mg/dL decreased CRP levels, with a marginally significant trend (Ptrend = 0.05).ConclusionsHigher Klotho concentrations were associated with reduced hyperlipidemia risk and triglyceride levels. Klotho supplementation maybe a promising method to intervene and prevent hyperlipidemia, but the underlying mechanism should be further explored.

Association between serum Klotho concentration and hypertension in postmenopausal women, a cross-sectional study from NHANES 2013–2016

BackgroundThe objective of this study was to examine the correlation between serum Klotho protein concentration and postmenopausal hypertension.MethodsA cross-sectional study design was used, in which 1713 postmenopausal women who participated in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 were included. Multivariate logistic regression models were applied to assess the association between serum Klotho concentration and postmenopausal hypertension.ResultsA weighted analysis was executed, revealing a noteworthy hypertension prevalence rate of 53.44% among the study participants. Participants with lower quartile of serum Klotho concentration had a higher prevalence of hypertension than those in higher quartiles (Q1:62.29% vs. Q2: 48.52% vs. Q3: 47.33% vs. Q4: 55.02%, p < 0.001). Furthermore, a multivariate logistic regression analysis confirmed that participants with higher quartiles of serum Klotho concentration had a significantly reduced risk of postmenopausal hypertension compared to those in the lowest quartile. Subgroup analysis displayed consistent findings in those following subgroups: aged ≥ 65 years, obesity, nonsmokers, individuals without diabetes and coronary heart disease, and those with higher levels of estradiol and estimated glomerular filtration rate. Based on the results, we concluded that there is a significant association between serum Klotho concentration and postmenopausal hypertension.ConclusionThe findings of this study revealed a significant inverse association between serum Klotho concentration and hypertension among postmenopausal women. Serum Klotho concentration may serve as a valuable biomarker for risk stratification in postmenopausal women who are at risk of developing hypertension.

Relationships between serum Klotho concentrations and cognitive performance among older chronic kidney disease patients with albuminuria in NHANES 2011-2014.

The potential relationship between Klotho and cognitive function is limited and controversial. This study aimed to quantify the association of Klotho and cognitive impairment in chronic kidney disease (CKD) patients with albuminuria. Serum Klotho was measured by enzyme-linked immunosorbent assay. Patients with urine albumin to creatinine ratio (UACR) > 30mg/g from the National Health and Nutrition Survey (NHANES) 2011-2014 were divided into 4 groups according to the quartile of Klotho. Cognitive function was examined using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Digit Symbol Substitution Test (DSST), and Animal Fluency Test. The relationship between Klotho and cognitive function was analyzed by multivariable regression and subgroup analysis. Among 368 CKD patients with albuminuria, we found that Klotho was negatively associated with creatinine, and positively associated with hemoglobin, and estimated glomerular filtration rate. No significant linear relationship was showed between Klotho (as a continuous variable) and cognitive function. When regarded Klotho as a category variable, patients in the quartile 3 group were at a better cognitive performance for CEARD-word learning subset and DSST, especially in the CKD patients with 30 mg/g < UACR <300 mg/g, but not in participants with UACR > 300 mg/g. The increased Klotho was associated with an increased cognitive function in CKD patients with microalbuminuria. Further studies are needed to demonstrate whether Klotho may be a beneficial biomarker of cognitive health and neurodegeneration.

Klotho reduces the risk of osteoporosis in postmenopausal women: a cross-sectional study of the National Health and Nutrition Examination Survey (NHANES)

BackgroundOsteoporosis (OP) is one of the diseases that endanger the health of the elderly population. Klotho protein is a hormone with anti-aging effects. A few studies have discussed the relationship between Klotho and OP. However, there is still a lack of research on larger populations. This study aims to evaluate the association between OP and Klotho in American postmenopausal women.MethodsThis is a retrospective study. We searched the National Health and Nutrition Examination Survey (NHANES) database and collected data of 3 survey cycles, finally involving 871 postmenopausal women over 50 years old in the present study. All participants took dual-energy X-ray absorptiometry examination and serum Klotho testing at the time of investigation. After adjusting the possible confounding variables, a multivariate regression model was employed to estimate the relationship between OP and Klotho proteins. Besides, the P for trend and restricted cubic spline (RCS) were applied to examine the threshold effect and calculate the inflection point.ResultsFactors influencing the occurrence of OP included age, ethnicity, body mass index and Klotho levels. Multivariate regression analysis indicated that the serum Klotho concentration was lower in OP patients than that in participants without OP (OR[log2Klotho] = 0.568, P = 0.027). The C-index of the prediction model built was 0.765, indicating good prediction performance. After adjusting the above-mentioned four variables, P values for trend showed significant differences between groups. RCSs revealed that when the Klotho concentration reached 824.09 pg/ml, the risk of OP decreased drastically.ConclusionBased on the analysis of the data collected from the NHANES database, we propose a correlation between Klotho and postmenopausal OP. A higher serum Klotho level is related to a lower incidence of OP. The findings of the present study can provide guidance for research on diagnosis and risk assessment of OP.

Change in circulating klotho in response to weight loss, with and without exercise, in adults with overweight or obesity.

Introduction: Klotho is a protein associated with protection from aging-related diseases and health conditions. Obesity is associated with lower Klotho concentrations. Thus, this secondary analysis of adults with obesity examined 1) the change in serum Klotho concentration in response to a behavioral weight loss intervention by the magnitude of weight loss achieved; and 2) the association among serum Klotho concentration and weight, body composition, and cardiorespiratory fitness. Methods: Participants were randomized to either diet alone (DIET), diet plus 150min of physical activity per week (DIET + PA150), or diet plus 250min of physical activity per week (DIET + PA250). Participants [n = 152; age: 45.0 ± 7.9years; body mass index (BMI): 32.4 ± 3.8kg/m2] included in this secondary analysis provided blood samples at baseline, 6-, and 12months, and were classified by weight loss response (Responder: achieved ≥10% weight loss at 6 or 12months; Non-responder: achieved <5% weight loss at both 6 and 12months). Serum Klotho was measured using a solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Analyses of covariance (ANCOVA's) were used to examine changes in weight, body composition, cardiorespiratory fitness, and Klotho concentration by weight loss response across the 12-month weight loss intervention. Results: Responders had a greater reduction in measures of weight and body composition, and a greater increase in cardiorespiratory fitness, compared to Non-Responders (p < 0.05). Change in Klotho concentration differed between Responders and Non-Responders (p < 0.05), with the increase in Klotho concentration from baseline to 6months for Responders being statistically significant. The 6-month change in Klotho concentration was inversely associated with the 6-month change in weight (r s = -0.195), BMI (r s = -0.196), fat mass (r s = -0.184), and waist circumference (r s = -0.218) (p-values <0.05). Discussion: Findings provide evidence within the context of a behavioral intervention, with and without exercise, that change in Klotho concentration is significantly different between adults with weight loss ≥10% compared to <5% across 12months. These findings suggest that weight loss and reduction in fat mass may be favorably associated with the change in Klotho concentration. This may reduce the risk of negative health consequences associated with accelerated aging in middle-aged adults.

Analysis of the association between serum antiaging humoral factor klotho and cardiovascular disease potential risk factor apolipoprotein B in general population.

Cardiovascular disease (CVD) is a prevalent health issue, and various risk factors contribute to its development, including blood lipids, blood pressure, diabetes, smoking, and alcohol consumption. Apolipoprotein B (ApoB) is related to CVD. ApoB is present on the surface of low-density lipoprotein (LDL), and its cellular recognition and LDL uptake are mainly achieved through recognition. It plays a crucial role in the diagnosis and treatment of CVD. This study aims to investigate the relationship between Klotho and ApoB in the general population of the United States as the correlation between serum Klotho and apoB is currently unknown. These findings could potentially guide the development of future treatments for CVD. This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2016. A linear regression model and smooth curve fitting were conducted to analyze the relationship between serum Klotho and apoB. The results indicate a negative correlation between serum Klotho concentration and apoB concentration (β = -71.7; 95% confidence interval [CI]: -120.8, -22.6; P = .005). After adjusting for confounding variables, the negative correlation between apoB concentration and serum Klotho concentration became more significant (β = -91.8; 95% CI: -151.3, -32.2; P = .004). When apoB concentration was converted from a continuous variable to a categorical variable (tertiles: T1 <0.8 g/L; T2: ≥0.8 g/L to <1.0 g/L; T3: ≥1.0 g/L), the serum klotho level of participants in the highest tertile (≥1.0 g/L) was -44.8 pg/mL (95% CI: -86.3, -3.2; P = .040) lower than that in the lowest tertile (<0.8 g/L). The smooth curve fitting diagram revealed differences in the relationship between serum Klotho concentration and apoB among individuals with different CVD risk factors. This study demonstrates a significant negative correlation between serum Klotho concentration and apoB concentration, even after controlling for confounding factors. The findings suggest that serum Klotho and apoB may be involved in the development of CVD, and targeting these factors could be a potential approach for CVD prevention and treatment.