Serum Klotho Research Articles

Associations of Klotho protein level and blood lipid parameters with carotid atherosclerosis in men

Aim of the study was to investigate the association of serum Klotho protein content and lipid parameters with atherosclerosis of the brachiocephalic arteries (BCA) in men.Material and methods. A cross-sectional comparative study that included men aged 50–65 years (n = 63, age 54 [53; 60] years (median [lower quartile; upper quartile])) underwent ultrasound examination of BCA at the outpatient department of the Institute of Internal and Preventive Medicine. Biochemical parameters were determined by standard enzymatic methods. Serum concentration of Klotho protein was measured by enzyme immunoassay.Results. A trend towards content of Klotho protein in serum was found in the group of persons with BCA atherosclerosis compared to the group without BCA atherosclerosis (705 [463; 1255] and 447 [282; 881] pg/ml, respectively, p = 0.061). Also, in men of this group, higher level of triglycerides (TG) (1.7 [1.1; 2.2] and 1.4 [0.9; 1.8] mmol/l, p = 0.046) and lower high-density lipoprotein cholesterol (HDL-C) content (1.1 [0.8; 1.3] m 1.4 [0.9; 1.6] mmol/l, p = 0.016) has been found. Correlation analysis in the group of men with BCA atherosclerosis revealed a direct relationship of Klotho protein with TG level (0.290; p = 0.031) and a negative relationship with HDL-C content (–0.361; p = 0.046). The results of logistic regression analysis showed that the probability of atherosclerotic plaques presence in BCA increased by 1.2 times (95 % confidence interval (95 % CI) 1.0–1.4, p = 0.038) with increasing age and by 9.2 times (95 % CI 2, 3–36.5, p = 0.002) in the presence of hypertension.Conclusions. In a clinical sample of men aged 50–65 years, the relative risk of carotid atherosclerosis is directly associated with age and the presence of hypertension and is not associated with the level of Klotho serum protein.

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>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>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.

Relationship between klotho and physical function in healthy aging

Epidemiological studies have reported a strong association between circulating Klotho and physical function; however, the cohorts were comprised of older adults with multiple comorbidities. Herein, we examined the relationship between Klotho and physical function in a community-based cohort of healthy adults. In this cross-sectional study, serum Klotho was measured in 80 adults who visited the Musculoskeletal Function, Imaging, and Tissue Resource Core of the Indiana Center for Musculoskeletal Health. Participants (n = 20, 10 [50%] men per group) were chosen into four age groups: 20–34, 35–49, 50–64, and ≥ 65 years, and were further grouped based on performance (low vs. high) on grip strength and chair stand tests. Klotho levels were lower in the ≥ 65 years group (703.0 [189.3] pg/mL; p = 0.022) and the 50–64 years group (722.6 [190.5] pg/mL; p = 0.045) compared to 20–34 years (916.1 [284.8] pg/mL). No differences were observed in Klotho between the low and high performers. The ≥ 65 years group walked a shorter distance during the 6-min walk test (6MWT) compared to 20–34 years (p = 0.005). Klotho was correlated with age (p < 0.001), body fat (p = 0.037), and 6MWT distance (p = 0.022). Klotho levels decline as early as the fifth decade of life, potentially before the onset of age-related impairment in exercise capacity.

U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population: a cross-sectional study

BackgroundPhenotypic age acceleration, which reflects the difference between phenotypic age and chronological age, is an assessment to measure accelerated aging. Klotho is a protein related to slower aging, but its association with accelerated aging remains unclear.MethodsBased on data from the 2007–2010 National Health and Nutrition Examination Survey, phenotypic age was calculated using chronological age and 9 aging-related biomarkers. A total of 4388 participants aged 40 to 79 years with measured serum Klotho and calculated phenotypic age were enrolled. The association between serum Klotho and phenotypic age acceleration was estimated using multivariable linear regression models. The possible nonlinear relationship was examined with smooth curve fitting. We also conducted a segmented regression model to examine the threshold effect.ResultsThe association between serum Klotho and phenotypic age acceleration followed a U-shaped curve (p for nonlinearity < 0.001), with the inflection point at 870.7 pg/ml. The phenotypic age acceleration significantly decreased with the increment of serum Klotho (per SD increment: β -1.77; 95% CI, -2.57 ~ -0.98) in participants with serum Klotho < 870.7 pg/ml, and increased with the increment of serum Klotho (per SD increment:β, 1.03; 95% CI: 0.53 ~ 1.54) in participants with serum Klotho ≥ 870.7 pg/ml.ConclusionThere was a U-shaped association between serum Klotho and accelerated aging among the middle-aged and elderly US population.

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.

Effect of recombinant human growth hormone on serum Klotho and fibroblast growth factor 23 in children with idiopathic short stature

To investigate the changes in the serum levels of Klotho, fibroblast growth factor 23 (FGF23), and insulin-like growth factor-1 (IGF-1) in children with idiopathic short stature (ISS) before and after recombinant human growth hormone (rhGH) treatment, as well as the correlation of Klotho and FGF23 with the growth hormone (GH)/IGF-1 growth axis in these children. A prospective study was conducted on 33 children who were diagnosed with ISS in the Department of Pediatrics, Hebei Provincial People's Hospital, from March 10, 2021 to December 1, 2022 (ISS group). Twenty-nine healthy children, matched for age and sex, who attended the Department of Child Healthcare during the same period, were enrolled as the healthy control group. The children in the ISS group were treated with rhGH, and the serum levels of Klotho, FGF23, and IGF-1 were measured before treatment and after 3, 6, and 9 months of treatment. A correlation analysis was conducted on these indexes. There were no significant differences in the serum levels of IGF-1, Klotho, and FGF23 between the ISS and healthy control groups (P>0.05). The serum levels of Klotho, FGF23, and IGF-1 increased significantly in the ISS group after 3, 6, and 9 months of rhGH treatment (P<0.05). In the ISS group, Klotho and FGF23 levels were positively correlated with the phosphate level before treatment (P<0.05). Before treatment and after 3, 6, and 9 months of rhGH treatment, the Klotho level was positively correlated with the IGF-1 level (P<0.05), the FGF23 level was positively correlated with the IGF-1 level (P<0.05), and the Klotho level was positively correlated with the FGF23 level (P<0.05), while Klotho and FGF23 levels were not correlated with the height standard deviation of point (P>0.05). The rhGH treatment can upregulate the levels of Klotho, FGF23, and IGF-1 and realize the catch-up growth in children with ISS. Klotho and FGF23 may not directly promote the linear growth of children with ISS, but may have indirect effects through the pathways such as IGF-1 and phosphate metabolism. The consistent changes in Klotho, FGF23 and IGF-1 levels show that there is a synergistic relationship among them in regulating the linear growth of ISS children.

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.

Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group.

Klotho, a multifunctional protein, acts as a co-receptor in fibroblast growth factor 23 and exerts its impact through various molecular pathways, including Wnt, hypoxia-inducible factor and insulin-like growth factor 1 pathways. The physiological significance of Klotho is the regulation of vitamin D and phosphate metabolism as well as serving as a vital component in aging and neurodegeneration. The role of Klotho in aging and neurodegeneration in particular has gained considerable attention. In this narrative review we highlight several key insights into the molecular basis and physiological function of Klotho and synthesize current research on the role of Klotho in neurodegeneration and aging. Klotho deficiency was associated with cognitive impairment, reduced growth, diminished longevity and the development of age-related diseases in vivo. Serum Klotho levels showed a decline in individuals with advanced age and those affected by chronic kidney disease, establishing its potential diagnostic significance. Additionally, multiple medications have been demonstrated to influence Klotho levels. Therefore, this comprehensive review suggests that Klotho could open the door to novel interventions aimed at addressing the challenges of aging and neurodegenerative disorders.

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 Relationship Between Serum Fibroblast Growth Factor 23 and Klotho Protein and Low Bone Mineral Density in Middle-Aged and Elderly Patients with End-Stage Renal Disease.

To assess the correlation between serum fibroblast growth factor 23 (FGF-23)/Klotho levels and end-stage renal disease (ESRD) in middle-aged and elderly patients combined with low bone mineral density (BMD). The BMD of the lumbar vertebrae and femoral neck of 87 patients with ESRD was measured using a dual-energy X-ray bone densitometer during hospitalisation and the patients were divided into a normal bone mass group and a low bone mass group. Haemoglobin, albumin, urea nitrogen, uric acid, creatinine, low-density lipoprotein cholesterol, alkaline phosphatase, blood calcium, blood phosphorus and full parathyroid hormone were detected using an automatic biochemical analyser. The levels of serum FGF-23, Klotho and activated vitamin D in the patients with ESRD were measured via an enzyme-linked immunosorbent assay. Older age and decreased serum creatinine levels and serum Klotho levels were associated with low bone mass. There were significantly more men in normal bone mass group (n=49, 74.24%) than in low bone mass group (n=8, 38.10%). The correlation analysis showed that BMD was negatively correlated with age but positively correlated with serum Klotho. The binary logistic regression analysis indicated that old age and the decrease in serum Klotho level were independent risk factors of a low BMD (all p<0.05). In conclusion, serum Klotho is closely related to BMD changes in middle-aged and elderly patients with ESRD. A high Klotho level is a protective factor and is expected to be a marker in reducing bone mineral metabolism disorders and improving the prognosis of patients with ESRD.

Lower serum Klotho level and higher systemic immune-inflammation index: an inverse correlation

ObjectivesKlotho, an anti-aging protein, has been identified to control tissue inflammatory responses. The objective of this research is to determine the linkage between soluble Klotho (S-Klotho) level and systemic immune-inflammation index (SII).MethodsEligible participants with complete information of S-Klotho level and SII were selected from the National Health and Nutrition Examination Surveys (NHANES). Subsequently, weighted multivariate linear regression and subgroup analysis were carried out to evaluate the association.ResultsTotally, 11,108 adults with complete data on S-Klotho level, SII and other important covariates were included in final analysis. Multivariate liner regression revealed that high level of S-Klotho was associated with low level of SII after multivariate adjustments (β=-0.08, 95%CI:-0.10- -0.05, P < 0.01). When classifying S-Klotho into tertiles, participants in S-Klotho tertile 3 (Q3) showed a decrease in SII level compared with those in the lowest tertile (Q1) (β=-45.44, 95%CI:-64.41- -26.47, P < 0.01 ). The negative associations remained significant regardless of age and gender, and varied depending on smoking status and BMI subgroups.ConclusionS-Klotho level was negatively related to SII after controlling for covariates. Further studies need to validate current findings and explore the fundamental mechanisms.

A novel U-shaped relationship between serum klotho and abdominal aortic calcification in the general population.

Abdominal aortic calcification (AAC) is considered an independent predictor of cardiovascular morbidity and mortality. Klotho, an anti-aging gene, has cardiovascular protective effects. At present, the association between klotho and AAC in the general population is uncertain. We investigated the relationship between serum soluble α-klotho (SSKL) and AAC in 2 327 participants from the National Health and Nutrition Examination Survey. To estimate the association between log-transformed SSKL (lnSSKL) and AAC, multivariate logistic regression analyses were conducted. Stratified analyses were performed to evaluated the potential modifiers. Smoothed curve fitting and generalised additive models were also performed. We found lnSSKL correlated negatively with AAC after adjusting for other confounders. The relationship of lnSSKL with AAC was a U-shaped curve (inflection point: 7.01 pg/ml). On subgroup analyses, stratified by age and smoking habit, the negative correlation of lnSSKL with AAC remained in men and in the population who smoked. Our study revealed a negative relationship between lnSSKL and AAC in the general population. This relationship showed a U-shaped curve and was influenced by age and smoking habit.

The association of serum neurofilament light chains with early symptoms related to Parkinson's disease: A cross-sectional study

Neurofilament light chains (NfL), released with neural axon injury, is considered as a potential biomarker for Parkinson's disease (PD). The relationship between NfL and PD has been studied mainly in diagnosed patients. Few large-scale studies analyze the association between NfL levels and multiple non-motor symptoms linked to early PD in the general population. Therefore, this study aims to determine the association of NfL with early symptoms of PD, and effectively respond to the development of early symptoms of PD. We examined the relationship between serum NfL and early non-motor symptoms of PD (smell dysfunction, sleep problems, cognitive function) and serum Klotho levels in the general population using data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). The relationship between serum NfL and early symptoms of PD in 1125 participants was analyzed by multiple linear regression and logistic regression models. The results showed a significant association between serum NfL and early symptoms of PD. There was a significant positive correlation between NfL and smell dysfunction, short sleep and long sleep. There was a significant negative correlation between NfL and Klotho levels and cognitive function test results. Further, we observed gender and age differences in the association of NfL with early symptoms of PD. Our study demonstrate that elevated serum NfL levels are positively associated with an increased risk of early PD-related symptoms, suggesting that serum NfL can be a promising biomarker for early PD.

Association between daily alcohol consumption and serum alpha klotho levels among U.S. adults over 40 years old: a cross-sectional study

BackgroundKlotho is a hormone considered to be an anti-aging biomarker. The relationships between daily alcohol consumption and serum klotho are mainly unknown. The purpose of this study is to assess the relationship between alcohol consumption and serum alpha klotho (α−klotho) levels in the U.S.MethodsThe data came from 11,558 participants aged ≥ 40 in the 2007−2016 National Health and Nutrition Examination Survey. Adults with reliable α−klotho plasma results were the target population. The self-report method was used to assess alcohol consumption. The relationship between daily alcohol intake and serum α−klotho levels was estimated using multivariable linear regression models. We also performed a stratified analysis of clinically important variables.ResultsThe mean serum α−klotho level among the 11,558 participants was 843.82 pg/mL. After full adjustment, participants with current moderate and heavy alcohol intake had lower serum α−klotho levels than those who never alcohol intake (β = − 62.64; 95% CI: − 88.86, − 36.43; P < 0.001; β = − 81.54; 95% CI: − 111.54, − 51.54; P < 0.001, respectively). Furthermore, the stratified analysis indicated that the association was insignificant in individuals with cardiovascular disease, chronic kidney disease, or cancer.ConclusionDaily alcohol consumption was inversely associated with serum α−klotho levels among U.S. adults over 40 years old. However, individuals with cardiovascular disease, chronic kidney disease, or cancer found no such relationship.

Serum Klotho Level and its Related Factors Among Male Opioids Addicts With Normal Renal Function Compared to Healthy Male Non-smokers and Smokers in Tabriz, Iran

Background: Klotho is an aging-suppressor gene that encodes a single-pass transmembrane protein and acts as a hormone. In this study, we aim to investigate the serum α-Klotho level in male opioids addicts with normal kidney function compared to healthy male non-smokers and smokers in Tabriz, Iran. Methods: Participnts were 87 men with normal kidney function referred to Sina Educational Research and Treatment Center in Tabriz, Iran (29 opioids addicts, 29 healthy non-smokers, and 29 healthy smokers). Blood samples were collected to measure the soluble a-Klotho level using an ELISA kit. Furthermore, blood creatinine (Cr) and hemoglobin (Hb) levels was measured. Body mass index (BMI) was also calculated for all participants. Results: In addicts, BMI, Hb, and Cr levels were significantly lower than in healthy non-smokers and smokers, but their Klotho level was higher (P&gt;0.05). The Klotho level in healthy smokers was significantly lower than in healthy non-smokers and addicts. The Klotho level of healthy smokers decreased as the pack year increased, but the duration of opioid addiction had no significant association with the Klotho level. There was no significant difference in the Klotho level between control groups (non-smokers and smokers) and men with addiction to different types of opioids. Conclusion: The Klotho level in male opioid addicts is significantly higher than in smokers. There is a significant negative correlation between BMI and Klotho levels among men with normal BMI and overweight. Further studies are recommended in these fields.

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.

The relationship between klotho, testosterone, and sexual health parameters among US adult men.

Klotho is a pleotropic hormone involved in a multitude of biological processes necessary for healthy aging, and affords protection from adverse events such as cardiovascular disease, inflammation, and various cancers. Emerging evidence suggests that klotho is also an important component of biochemical pathways that regulate hormone balance, which may include those pathways governing testosterone production and men's sexual health, though data are limited and results are mixed. Using a cohort of 767 men from the NHANES 2015-2016 survey cycle, we set out to quantify the association between serum klotho levels and serum testosterone levels, as well as clinical markers of men's sexual health (e.g., testosterone:estrogen ratio, bioavailable testosterone, and free testosterone). Multivariable linear and logistic regression models while controlling for potential confounders were constructed to quantify the relationship between serum klotho and testosterone, as well as between serum klotho and odds of low testosterone (serum testosterone < 300ng/dL). A positive association was observed between serum klotho and testosterone (β = 0.18, p = 0.04). Serum klotho levels were also stratified into quartiles, and we observed statisticallysignificant increases in testosterone for increasing quartile level of klotho using the first quartile as the reference group (β = 90.51, p = 0.001, β = 106.93, p = 0.002, β = 95.33, p = 0.03 for quartiles 2, 3, and 4, respectively). The average testosterone values by quartiles of klotho were 306.9ng/dL, 390ng/dL, 409.3ng/dL, and 436.6ng/dL, respectively. We modeled important proxies for sexual health including bioavailable and free testosterone, the testosterone:estradiol ratio, and C-reactive protein. Men in the second quartile of klotho had a significantly lower odds of an abnormal testosterone:estradiol ratio compared to the first quartile [OR = 0.18, 95% CI = (0.03, 0.98)].We observed null associations between continuous serum klotho and odds of low testosterone [OR = 1.0, 95% CI = (1.0, 1.0)], and when stratified by quartile, we observed a significant decrease in the odds of low testosterone for individuals in the second quartile of klotho compared to the first quartile [OR = 0.21, 95% CI = (0.05, 0.91)]. In addition, C-reactive protein was inversely associated with testosterone in men (β = - 4.65, p = 0.001), and inversely associated with quartiles of klotho (β = - 2.28, p = 0.04, β = - 2.22, p = 0.04, β = - 2.28, p = 0.03, for quartiles 2, 3, and 4, respectively). Our findings support previous studies suggesting a role for klotho in testosterone levels and sexual function among men. Future studies are warranted to corroborate these findings, determine clinical significance, and elucidate potential mechanisms underlying these associations.

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.