Serum α-Klotho Research Articles

Serum alpha klotho levels in Parkinson's Disease.

Parkinson's Disease (PD), a neurodegenerative disorder, is associated with substantial morbidity. α-Klotho, an anti-aging protein known for its neuroprotective properties, has gained attention. This study aims to assess serum levels of α-Klotho in PD patients. This study is a cross-sectional case-control study. PD was diagnosed according to UK Parkinson Disease Society Brain Bank criteria. Serum α-Klotho level was measured using a commercially available enzyme-linked immunosorbent assay. Of the 314 participants in the study, 157 were patients with PD and 157 were controls. Lower levels of α-Klotho were observed in PD (0.85 nmol/L) in comparison to the controls (1.47 nmol/L, p < 0.001). α-Klotho levels were also significantly lower among PD patients with dementia compared to PD patients without dementia. In logistic regression analysis, α-Klotho (OR: 0.04, p < 0.001) demonstrated a significant relationship between PD. A significant correlation was identified between α-Klotho levels and Mini-Mental State Examination scores in PD patients. The sensitivity and the specifity of α-Klotho were 90% and 65% for predicting PD. Our findings suggest that α-klotho could potentially serve as a biomarker. However additional studies are needed to confirm our findings.

α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage3band 4 chronic kidney disease(CKD): a long-term prospective cohort study.

α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. In this prospective study, 75 non-diabetic CKD stage 3b-4 patients werefollowed-up for a median of 8years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols.All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcificationof the abdominal aorta.Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC)by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. In pre-dialysis CKD patients, α-Klotho levels areassociated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

The association between serum soluble α-Klotho and thyroid profile among adults from NHANES 2007–2012

BackgroundThyroid hormone is the key endocrine regulator of growth, development, metabolism, and other bodily functions. α-Klotho has been involved in the aging process and acts as an endocrine factor involved in the regulation of various metabolic processes in humans. However, the relationship between α-Klotho and thyroid profile has not been uniformly recognize.ObjectiveTo determine the relationship between α-Klotho and thyroid profile in adult individuals.MethodsPopulation data of 4614 adult individuals were obtained from the NHANES database during the period of 2007–2012. Weighted multivariable regression analysis was performed using a general linear model with serum α-Klotho as the independent variable and thyroid profile as the dependent variables, respectively. The generalized additive model was used for smoothing curve fitting and threshold effect analysis.Resultsα-Klotho was associated with a slightly higher FT3, TT3 and TT4 level in unadjusted and adjusted regression models. However, a higher α-Klotho level was associated with a lower TSH level. After α-Klotho was grouped as quantiles with reference (Q1), α-Klotho still showed a statistically significant positive correlation with FT3 and TT3 levels in Q2, Q3 and Q4. In addition, α-Klotho was positively corrected with TT4, but negatively associated with TSH in Q4.ConclusionsSerum soluble α-Klotho was positively associated with FT3, TT3 and TT4, but negatively correlated with TSH. The significant effect of α-Klotho on thyroid profile suggests its potential as a predictive marker of thyroid functions, indicating its possible involvement in the regulation of thyroid hormone secretion.

Serum α-Klotho with all-cause and cause-specific mortality.

The relationship between α-Klotho (αK) and mortality is controversial and has not been examined in a large, diverse cohort. We investigated the association between serum αK protein levels with all-cause and cause-specific mortality in a cohort representative of the US population. We used National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016. A nonlinear association between mortality and αK levels as a quadratic variable were examined using Cox proportional hazard models and competing risk models. Multivariable models were adjusted for age, gender, race, hypertension, diabetes, smoking, alcohol use, physical activity, body mass index (BMI), serum cholesterol, estimated glomerular filtration rate, highest educational status attained and family income to poverty threshold ratio. Of the 13 749 participants, 1569 (11%) died, 7092 (52%) were female, and 5918 (43%) were Caucasian. The mean (SD) of age was 58 (11) years, BMI 29.7 (6.7) kg/m2, and αK was 0.85 (0.31) ng/mL. In the adjusted Cox proportional hazards model with quadratic αK, we found a U-shaped relationship between all-cause mortality and αK levels (continuous αK hazard ratio [HR] = 0.56, 95% confidence interval [CI]: 0.37, 0.85; P = .007; squared-αK HR = 1.25, 95% CI: 1.11, 1.41; P < 0.001). A similar U-shaped relationship was noted between αK and cancer mortality in the adjusted Cox proportional hazards model (continuous αK HR = 0.45, 95% CI: 0.19, 1.06; P = 0.07; squared αK HR = 1.32, 95% CI: 1.07, 1.61; P = 0.009). No relationship was present with cardiovascular or other-cause mortality. In this large diverse cohort, we report a U-shaped relationship between αK with all-cause and cancer mortality. Further research to elucidate the underlying biological mechanism of these relationships is needed.

Association between weight change and serum anti-aging protein α-Klotho: a cross-sectional study in middle-aged and older adults

The relationship of weight change has extended to accelerated ageing, yet little is known about the association between weight change and anti-aging protein α-Klotho. This study included 10,972 subjects from the National Health and Nutrition Examination Survey 2007–2016. Participants were measured body weight and height at baseline and recalled weight at young adulthood and middle adulthood. α-Klotho concentrations were quantified. Generalized linear regression models were used to assess the association between weight change and α-Klotho. Across adulthood, maximal overweight, non-obese to obese, and stable obesity were consistently associated with lower serum Klotho levels. Compared with participants who remained at normal weight, from middle to late adulthood, participants experiencing maximal overweight, moving from the non-obese to obese, and maintaining obesity had 27.97 (95% CI: − 46.57 to − 9.36), 39.16 (95% CI: − 61.15 to − 17.18), and 34.55 (95% CI: − 55.73 to − 13.37) pg/ml lower α-Klotho, respectively; similarly, from young to late adulthood, those had 29.21 (95% CI: − 47.00 to − 11.42) , 34.14 (95% CI: − 52.88 to − 15.40), and 36.61 (95% CI: − 65.01 to − 8.21) lower, respectively. Interestingly, from middle to late adulthood, the absolute weight change values of 590 participants who changed from obese to non-obese were negatively associated with serum α-Klotho. Each 1 kg of weight loss during the process of changing from obese to non-obese brought about a relative increase in α-Klotho levels of 3.03 pg/ml. The findings suggest the potential role of weight management across adulthood for aging.

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.

Deciphering the Biological Aging Impact on Alveolar Bone Loss: Insights From α-Klotho and Renal Function Dynamics.

Alveolar bone loss is generally considered a chronological age-related disease. As biological aging process is not absolutely determined by increasing age, whether alveolar bone loss is associated with increasing chronological age or biological aging remains unclear. Accurately distinguishing whether alveolar bone loss is chronological age-related or biological aging-related is critical for selecting appropriate clinical treatments. This study aimed to identify the relationship between alveolar bone loss and body aging. In total, 3635 participants from the National Health and Nutrition Examination Survey and 71 living kidney transplant recipients from Gene Expression Omnibus Datasets were enrolled. Multivariate regression analysis, smooth curve fittings, and generalized additive models were used to explore the association among alveolar bone loss, age, serum α-Klotho level, renal function markers, as well as between preoperative creatinine and renal cortex-related α-Klotho gene expression level. Meanwhile, a 2-sample Mendelian randomization (MR) study was conducted to assess the causal relationship between α-Klotho and periodontal disease (4 376 individuals vs 361 194 individuals). As a biological aging-related indicator, the α-Klotho level was negatively correlated with impaired renal function and alveolar bone loss. Correspondingly, accompanied by decreasing renal function, it was manifested with a downregulated expression level of α-Klotho in the renal cortex and aggravated alveolar bone loss. The MR analysis further identified the negative association between higher genetically predicted α-Klotho concentrations with alveolar bone loss susceptibility using the IVW (odds ratio [OR] = 0.999, p = .005). However, an inversely U-shaped association was observed between chronological age and alveolar bone loss, which is especially stable in men (the optimal cutoff values were both 62 years old). For men above 62 years old, increasing age is converted to protective factor and is accompanied by alleviated alveolar bone loss. Alveolar bone loss that is directly associated with decreased renal function and α-Klotho level was related to biological aging rather than chronological age. The renal-alveolar bone axis could provide a new sight of clinical therapy in alveolar bone loss.

Role of serum α-Klotho level in patients with breast carcinoma.

e15031 Background: The Klotho gene regulates multiple intracellular signalling pathways involving FGF-23, Insulin, IGF1, TGF-β1, Wnt/β-catenin and mammalian targets of rapamycin. The Klotho gene is downregulated in cancer and has a tumour suppressor role. Only a few studies have been done assessing its role in various cancers. None has looked into its association with all the clinicopathological characteristics of Carcinoma breast along with Pathological complete response (PCR). In August 2022, an oral senolytic form of Klotho was identified making it a possible and targetable protein. Methods: This was a Prospective cross-sectional study. Patients with biopsy-proven carcinoma breast who were previously untreated and had no significant past history were included. 84 patients were studied. Serum αKlotho level was estimated before initiating any treatment and its association with clinicopathological characteristics and with PCR was analysed. Results: A total of 84 patients were studied. The mean age was 50.76 years. Amongst our patients 65% were Estrogen Receptor (ER)+, 41.6% HER2+ and 11.9% were TNBC. 11.9% were of T1 stage, 29.8% T2, 19% T3, and 39.3% were T4. 16.7% had N0, 48.8% N1, 14.3% N2 and 20.2% had N3 stage. 20.2% were metastatic (MBC) and 79.8% were non-metastatic. 33.3% had grade 3 tumours, 56% grade 2 and 10.7% had grade 1. 61.9% were treated with NACT. The mean serum αKlotho level was 1.81ng/ml ranging from 0-5.15ng/ml. The αKlotho level was 2.04ng/ml in ER+ and 1.37ng/ml in ER-negative (p 0.011). As the Nottingham grade of the tumour increased from 1 to 3, αKlotho level decreased, with a mean value of 3.54ng/ml in grade 1, 1.71ng/ml in grade 2, and 1.42ng/ml in grade 3 (p 0.001). As the T stage increased from 1 to 4, αKlotho level decreased from 2.6ng/ml to 1.61ng/ml. Patients with N0 had a higher αKlotho of 2.92ng/ml, N1 had 1.64ng/ml, N2 1.79ng/ml, and N3 had 1.31ng/ml (p 0.001). MBC had a lower level of 1.47ng/ml than non-metastatic(1.9ng/ml). αKlotho level negatively correlated with ki67 with a correlation coefficient of -0.2. Among the patients who received NACT, we analysed 36 patients for the correlation with PCR. αKlotho level in patients who attained PCR was 1.58ng/ml and in those who did not attain PCR was 1.64ng/ml which was not significant. Conclusions: Klotho gene is identified to have a tumour suppressor role and its product αKlotho seems to have a protective role in Carcinoma breast. We found that patients with a higher serum αKlotho level had a lower histological grade(p 0.001) and a Node-negative (p 0.001) disease. Non-metastatic patients and patients with lower Ki 67 had high αKlotho levels. However, we could not find any significant association between αKlotho level and PCR. This is the first study with a large sample size done to look at the association of serum αKlotho with clinicopathological characteristics of carcinoma breast and that has found a significant association of αKlotho levels with higher grade and Node-negative disease.

Positive association of the anti-aging protein α-Klotho with insulin resistance and its inverse L-shaped relationship with glycaemic control in the middle-aged and elderly population.

α-Klotho has been linked to insulin resistance (IR) in basic research. However, experimental evidence is inconsistent, and there is a lack of data from human research. This study seeks to elucidate the association of α-Klotho with IR in a nationwide, multiracial population. A total of 5289 participants aged 40-79 years were included in the National Health and Nutrition Examination Survey (NHANES) spanning 2007-2016. Serum α-Klotho was measured using enzyme-linked immunosorbent assays (ELISA), and IR was evaluated by the homeostatic model assessment of insulin resistance (HOMA-IR). Weighted multivariate logistic and linear regression analysis, subgroup analysis stratified by demographic characteristics, medical condition or obesity status, and sensitivity analysis using propensity score matching (PSM) were performed. Restricted cubic splines (RCS) were performed to explore the nonlinear relationship. In the fully adjusted logistic regression model, a significant positive association was observed between log-transformed α-Klotho and IR (OR = 3.63, 95% CI: 1.56, 8.45), particularly in males or nonobese individuals (Pinteraction < 0.05). In the linear regression model, log10(α-Klotho) was associated with fasting blood glucose (FBG, β = 1.25, 95% CI: 0.74, 1.76) and glycosylated hemoglobin (HbA1c, β = 0.49, 95% CI: 0.20, 0.77). RCS revealed an inverse L-shaped dose-response relationship of α-Klotho with FBG and HbA1c (Pnonlinear <0.05). Beyond the inflection point of log10(α-Klotho) at 2.79, β coefficients sharply rose for these glycaemic control indicators. The study provides clinical evidence supporting a positive association between α-Klotho and IR. Moreover, the inverse L-shaped relationship suggests that α-Klotho should reach a certain level to predict glycaemic changes effectively.

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.

Circulating Levels of Soluble α-Klotho and FGF23 in Childhood Cancer Survivors: Lack of Association with Nephro- and Cardiotoxicity-A Preliminary Study.

Background/Objectives: The survival rate among pediatric cancer patients has reached 80%; however, these childhood cancer survivors (CCSs) are at a heightened risk of developing chronic conditions in adulthood, particularly kidney and cardiovascular diseases. The aims of this study were to assess the serum α-Klotho and FGF23 levels in CCSs and to determine their association with nephro- and cardiotoxicity. Methods: This study evaluated a cohort of 66 CCSs who remained in continuous remission, with a mean follow-up of 8.41 ± 3.76 years. Results: The results of this study revealed that CCSs exhibited significantly higher levels of soluble α-Klotho compared to healthy peers (1331.4 ± 735.5 pg/mL vs. 566.43 ± 157.7 pg/mL, p < 0.0001), while no significant difference was observed in their FGF23 levels. Within the participant cohort, eight individuals (12%) demonstrated a reduced estimated glomerular filtration rate (eGFR) below 90 mL/min/1.73 m2. The relationship between treatment with abdominal radiotherapy and reduced eGFR was confirmed (p < 0.05). No correlations were found between potential treatment-related risk factors, such as chemotherapy or radiation therapy, serum levels of α-Klotho and FGF23, and nephro- and cardiotoxicity. Conclusions: In conclusion, this preliminary cross-sectional study revealed elevated levels of α-Klotho among childhood cancer survivors but did not establish a direct association with anticancer treatment. The significance of elevated α-Klotho protein levels among CCSs warrants further investigation.

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.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

BackgroundCompelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).ObjectiveThis study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.MethodsSerum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.ResultsThis cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).ConclusionsT2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

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.

Fibroblast growth factor-23 and Alpha-Klotho concentrations in dogs with canine Leishmaniasis

This study aimed to assess the concentrations of Fibroblast Growth Factor-23 (FGF-23) and α-Klotho in healthy dogs and dogs at different stages of Canine Leishmaniasis (CanL), and investigate the changes of these parameters in relation to renal function and calcium‑phosphorus metabolism. A total of 74 dogs (22 healthy and 52 with CanL) of varying ages, sexes, and medium-sized breeds were included. Dogs with CanL were categorized into different stages (Stage I-IV) based on Leishvet recommendations. In addition to routine hematological parameters, plasma FGF-23, serum α-Klotho, urea, creatinine, phosphorus, calcium, parathormone, vitamin D concentrations, and urine protein/creatinine ratio were measured. Data from healthy dogs were compared to dogs with CanL overall and by stage. Dogs with CanL exhibited higher concentrations of FGF-23 (p < 0.05), α-Klotho, and parathormone (p < 0.001), as well as lower concentrations of vitamin D and calcium (p < 0.001). FGF-23 concentration was particularly elevated in Stage IV compared to other stages. However, no significant differences in α-Klotho levels were observed among the stages. FGF-23 levels showed a weak positive correlation with urea and creatinine concentrations and a moderate positive correlation with urine protein/creatinine ratio. This study demonstrated increased levels of FGF-23 and α-Klotho in dogs with CanL for the first time. The increase in FGF-23 levels was more prominent in advanced stages of the disease and correlated with higher urea and creatinine concentrations. These findings may serve as a basis for future diagnostic and therapeutic investigations, contributing to the understanding of the pathophysiology of kidney disease in CanL.

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.

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus.

Diabetic retinopathy is a commonly observed cause of blindness and is a common problem in individuals with diabetes. Recent investigations have showed the capability of serum α-Klotho and FGF 23 in mitigating the effects of diabetic retinopathy. This study aimed to discover the correlation between FGF 23, α-Klotho, and diabetic retinopathy in type 1 diabetics. This case-control study included 63 diabetic patients and 66 healthy controls. Following an overnight duration of fasting, morning blood samples were taken from both the patient and the control groups. The serum concentrations of α-Klotho and FGF 23 were quantified. An experienced ophthalmologist inspected the retinopathy. All participants in this study have moderate non-proliferative retinopathy. A p value under 0.05 was considered statistically significant. The mean α-Klotho level for retinopathic diabetic patients was 501.7 ± 172.2pg/mL and 579.6 ± 312.1pg/mL for non-retinopathic diabetic patients. In comparison, α-Klotho level of the control group was 523.2 ± 265.4pg/mL (p = 0.531). The mean of FGF 23 level did not demonstrate a significant difference (p = 0.259). The mean FGF 23 level were 75.7 ± 14.0pg/mL, 74.0 ± 14.8pg/mL and 79.3 ± 14.4pg/mL in groups, respectively. In conclusion, there was no significant difference in FGF 23 and α-Klotho levels between type 1 diabetics with and without retinopathy when compared to the control group.

Association between α-klotho levels and adults with COPD in the United States.

Chronic obstructive pulmonary disease (COPD) is accompanied by increased inflammation, persistent lung function decline, and extensive lung injury. Klotho, a well-known antiaging protein, has anti-inflammatory and antioxidative effects. However, the effects of klotho on COPD have yet to be thoroughly elucidated. This study examined the association among COPD adults and their α-klotho level. Data were collected from the 2007 to 2012 National Health and Nutrition Examination Survey (NHANES). A total of 676 participants were analyzed and divided into COPD (n = 403) and non-COPD (n = 273) groups. The two groups were compared with respect to clinical characteristics. Logistic regression analysis and a generalized additive model were used to estimate the association between COPD incidence and serum α-klotho concentration. All COPD participants were stratified according to the levels of α-klotho (Q1: <687 pg./mL; Q2: 687-900 pg./mL; Q3: ≥900 pg./mL), and clinical characteristics were compared. Non-COPD individuals had higher α-klotho levels than did COPD individuals (863.09 ± 267.13 vs. 817.51 ± 302.20, p < 0.05). Logistic regression analysis revealed that the Q2 and Q3 layers had a lower risk of COPD than did the Q1 layer, with odds ratios (ORs) of 0.73 (0.50, 0.99) for Q2 and 0.58 (0.41, 0.86) for Q3 (p < 0.001). The generalized additive model showed that the risk of COPD gradually decreased with increasing α-klotho concentration when the α-klotho concentration < 1,500 pg./mL, while the risk of COPD increased as the α-klotho concentration increased to ≥1,500 pg./mL. Compared with individuals in the Q2 or Q3 groups, individuals with COPD in the Q1 group were more likely to be current smokers, have lower levels of erythrocytes, and have higher levels of creatinine and leukocytes. Increased α-klotho levels were negatively correlated with the risk of COPD in participants over 40 years old with α-klotho <1,500 pg./mL. When α-klotho was ≥1,500 pg./mL, the risk of COPD increased as α-klotho levels increased. Pulmonary ventilation function and the number of hemocytes differed among COPD patients with different levels of α-klotho.