Klotho Levels Research Articles

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.

Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007–2012)

BackgroundKlotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet.MethodsLeveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations.ResultsThis study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman’s rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (β = 1.979 ppb and β = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The β coefficient for serum Klotho was 0.002 ppb/pg/ml.ConclusionsOur study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.

The Influence of Metabolic Syndrome on Potential Aging Biomarkers in Participants with Metabolic Syndrome Compared to Healthy Controls.

Biological aging is a physiological process that can be altered by various factors. The presence of a chronic metabolic disease can accelerate aging and increase the risk of further chronic diseases. The aim of the study was to determine whether the presence of metabolic syndrome (MetS) affects levels of markers that are associated with, among other things, aging. A total of 169 subjects (58 with MetS, and 111 without metabolic syndrome, i.e., non-MetS) participated in the study. Levels of telomerase, GDF11/15, sirtuin 1, follistatin, NLRP3, AGEs, klotho, DNA/RNA damage, NAD+, vitamin D, and blood lipids were assessed from blood samples using specific enzyme-linked immunosorbent assay (ELISA) kits. Telomerase (p < 0.01), DNA/RNA damage (p < 0.006) and GDF15 (p < 0.02) were higher in MetS group compared to non-MetS group. Only vitamin D levels were higher in the non-MetS group (p < 0.0002). Differences between MetS and non-MetS persons were also detected in groups divided according to age: in under 35-year-olds and those aged 35-50 years. Our results show that people with MetS compared to those without MetS have higher levels of some of the measured markers of biological aging. Thus, the presence of MetS may accelerate biological aging, which may be associated with an increased risk of chronic comorbidities that accompany MetS (cardiovascular, inflammatory, autoimmune, neurodegenerative, metabolic, or cancer diseases) and risk of premature death from all causes.

Retracted: Composite Dietary Antioxidant Index and Plasma Levels of Soluble Klotho: Insights from NHANES.

[This retracts the article DOI: 10.1155/2023/3524611.].

U-shaped association between serum Klotho and all-cause mortality in US cardiovascular patients: a prospective cohort study.

Increased levels of serum Klotho have been associated with a reduced risk of several cardiovascular diseases (CVD). However, limited studies exist on the association between serum Klotho and mortality in patients with CVD. We collected data from CVD patients in the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. We linked NHANES data with the National Death Index to determine the survival status of participants. Univariate and multivariable Cox regression models were used to investigate the relationship between serum Klotho levels and mortality in CVD patients. The relationship between serum Klotho quartiles and mortality in CVD patients was visualized using Kaplan-Meier (KM) curves and restricted cubic spine. Finally, subgroup analyses were used to examine the association between serum Klotho and all-cause mortality in different populations. 1905 patients with CVD were finally enrolled in our study with a mean follow-up of 7.1 years. The average age of the participants was 63.4 years, with 58.40% being male. KM showed that lower Klotho levels were associated with lower survival rates. After adjusting for potential confounders, patients with higher serum Klotho levels had lower all-cause mortality (Q1: 1.00, Q2: 0.58 (0.42-0.80), Q3: 0.69 (0.47-1.01), and Q4:0.64 (0.45-0.92). However, the relationship between serum Klotho levels and cardiovascular mortality was not statistically significant. Dose-response analysis shows a U-shaped relationship between serum Klotho levels and all-cause mortality in patients with CVD (Pnonlinear=0.002). Subgroup analysis indicated that participants with a history of hypertension had a higher risk of all-cause mortality in serum Klotho Q4 compared to Q1 (P trend <0.05). The relationship between serum Klotho levels and all-cause mortality in CVD patients exhibits a U-shaped association. The underlying mechanisms of this association need further investigation.

Serum FGF-23 and klotho levels in patients with systemic sclerosis and its relationship with carotid intima media thickness

Serum FGF-23 and klotho levels in patients with systemic sclerosis and its relationship with carotid intima media thickness

Molecular Interaction of Soluble Klotho with FGF23 in the Pathobiology of Aortic Valve Lesions Induced by Chronic Kidney Disease.

Chronic kidney disease (CKD) is linked to greater prevalence and rapid progression of calcific aortic valve disease (CAVD) characterized by valvular leaflet fibrosis and calcification. Fibroblast growth factor 23 (FGF23) level is elevated, and anti-aging protein Klotho is reduced in CKD patients. However, the roles of FGF23 and Klotho in the mechanism of aortic valve fibrosis and calcification remain unclear. We hypothesized that FGF23 mediates CKD-induced CAVD by enhancing aortic valve interstitial cell (AVIC) fibrosis and calcification, while soluble Klotho inhibits FGF23 effect. Methods and Results: In an old mouse model of CKD, kidney damages were accompanied by aortic valve thickening and calcification. FGF23 levels in plasma and aortic valve were increased, while Klotho levels were decreased. Recombinant FGF23 elevated the inflammatory, fibrogenic, and osteogenic activities in AVICs. Neutralizing antibody or shRNA targeting FGF23 suppressed the pathobiological activities in AVICs from valves affected by CAVD. FGF23 exerts its effects on AVICs via FGF receptor (FGFR)/Yes-associated protein (YAP) signaling, and inhibition of FGFR/YAP reduced FGF23's potency in AVICs. Recombinant Klotho downregulated the pathobiological activities in AVICs exposed to FGF23. Incubation of FGF23 with Klotho formed complexes and decreased FGF23's potency. Further, treatment of CKD mice with recombinant Klotho attenuated aortic valve lesions. Conclusion: This study demonstrates that CKD induces FGF23 accumulation, Klotho insufficiency and aortic valve lesions in old mice. FGF23 upregulates the inflammatory, fibrogenic and osteogenic activities in AVICs via the FGFR/YAP signaling pathway. Soluble Klotho suppresses FGF23 effect through molecular interaction and is capable of mitigating CKD-induced CAVD.

Association between serum Klotho levels and estimated pulse wave velocity in postmenopausal women: a cross-sectional study of NHANES 2007-2016.

Postmenopausal women are at an increased risk of arterial stiffness, which can be assessed using estimated pulse wave velocity (ePWV). This study aimed to investigate the relationship between serum klotho levels and ePWV in postmenopausal women. This cross-sectional study used data from postmenopausal women who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016. Participants were divided into two groups based on the presence of hypertension. Weighted multivariate linear regression was used to analyze the relationship between serum Klotho levels and ePWV in each group. Restricted cubic spline models with multivariable adjustments were employed to examine nonlinear associations within each group. Our analysis included 4,468 postmenopausal women from the NHANES database, with 1,671 in the non-hypertensive group and 2,797 in the hypertensive group. In all regression models, serum Klotho (ln-transformed) levels were significantly and independently negatively correlated with ePWV in the non-hypertensive group. After fully adjusting for confounders, a 1-unit increase in ln(Klotho) was associated with a 0.13m/s decrease in ePWV (β = -0.13, 95% CI -0.23 to -0.03; p = 0.008). Additionally, in the fully adjusted model, participants in the highest quartile of ln(Klotho) had an ePWV value 0.14m/s lower than those in the lowest quartile (p for trend = 0.017; 95% CI -0.23 to -0.05; p = 0.002). This negative correlation was consistent across subgroups and was particularly significant among women aged < 60 years, nonsmokers, and non-Hispanic Black women. However, no association was observed between serum Klotho levels and ePWV in the hypertensive group. Hypertension may affect the relationship between serum Klotho level and ePWV in postmenopausal women. Increased serum Klotho levels may reduce arterial stiffness in postmenopausal women. Further studies are required to confirm these findings.

Linear-inverse associations of serum Klotho protein with prevalence of frailty among adults in the United States.

To investigate the potential linear relationship between serum concentrations of klotho and frailty. A retrospective analysis was conducted on the data of 9,597 middle-aged and older adults (aged 40-79 years) from the five cycles of the National Health and Nutrition Examination Survey (NHANES). Frailty was assessed using the Frailty Index, calculated as a percentage of accumulated deficits across 53 health items. Restricted cubic spline curves, subgroup analyses and logistic regression models were employed to evaluate the specific linear trend connection between circulating klotho protein concentration and frailty. When taking Klotho into account as a continuous component in Models 1 and 2, there was a substantial association between the increasing Klotho level and the reduced risk of frailty. Model 3 revealed a strong negative correlation between the Klotho and Frailty, suggesting that high levels of Klotho protein decreases the frailty prevalence [Odd ratio (OR): 0.25; 95% confidence interval (CI): 0.15-0.43]. Furthermore, according to the quartile analyses, after fully adjusting for the covariates, it was observed that, comparing to the lowest quartile of Klotho, the highest quartile of Klotho demonstrated lowest risk of frailty (OR 0.69; 95% CI 0.58-0.81, Ptrend < 0.001). The restricted cubic spline curves showed a linear relationship and an inverse association between frailty and the Klotho levels (Plinearity < 0.001; Pnon-linearity = 0.736). Klotho is inversely and linearly associated with physical frailty in the general population (aged 40-79 years), specifically in the population with an age < 65 and body mass index (BMI) ≥ 25 kg/m2. More necessary prospective studies should be done to further investigate the mechanisms underlying frailty and aging and to elucidate individual frailty causes.

The Effect of Propofol on the Hippocampus in Chronic Cerebral Hypoxia in a Rat Model Through Klotho Regulation.

Chronic cerebral hypoxia often leads to brain damage and inflammation. Propofol is suggested to have neuroprotective effects under anaesthesia. This study used rat models with carotid artery coarctation or closure. Four groups of rats were compared: a control group, a propofol-treated group, a group with bilateral common carotid artery blockage (BCAO), and a BCAO group treated with propofol post-surgery. The Morris water maze test indicated cognitive impairment in BCAO rats, which also showed hippocampal structure changes, oxidative stress markers alteration, and reduced Klotho expression. Propofol treatment post-BCAO surgery improved these outcomes, suggesting its potential in mitigating chronic cerebral hypoxia effects. Propofol may increase klotho levels and reduce apoptosis and inflammation linked to oxidative stress in cognitively impaired mice.

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.

Association between Serum Klotho and All-Cause Mortality in Chronic Kidney Disease: Evidence from a Prospective Cohort Study

Plain Language SummaryChronic kidney disease (CKD) is a serious health condition where your kidneys do not work as they should. People with CKD face a higher risk of illness and even death. We wanted to know if a substance called Klotho in your blood might be connected to how long people with CKD live. We studied information from over 2,400 CKD patients. We followed them for almost 7 years to see what happened. We found that people with higher Klotho levels in their blood tend to live longer. It is like a good sign for their health. But we also discovered something interesting. The relationship between Klotho and survival is not simple. It is shaped like the letter “L.” Up to a certain point, higher Klotho levels mean a better chance of living longer. But after a certain level, having even more Klotho does not seem to make a difference. So, it is not just about having lots of Klotho; but about having the right amount. Our study helps us understand Klotho better and its connection to CKD. Knowing more about Klotho could help doctors find new ways to help people with CKD live longer and healthier lives. In plain words, having enough Klotho in your blood might be good for your health if you have CKD. But having too much does not seem to help any more than having just enough. This information could help doctors find better ways to treat people with CKD.

Causal Associations Between Plasma Protein Levels and Alzheimer Disease

AbstractBackgroundThe aim of this study was to infer causal relationships between protein levels measured in blood and the risk of late‐onset Alzheimer disease (AD).MethodTwo‐sample Mendelian randomization (MR) was used to infer the causal effect of protein levels on AD risk. Summary statistics from genome‐wide association studies (GWAS) for 4,907 SomaScan aptamers (measuring 4,719 proteins) from Ferkingstad et al. (2021) in 35,559 Icelanders (average age = 55±17years), and for AD GWAS from Bellenguez et al. (2022). Instruments for exposures were selected at p &lt; 5×10−8 and p &lt; 5×10−6 thresholds respectively for the main and sensitivity analyses. Instruments were pruned for linkage disequilibrium (r2 &lt; 0.0001) to ensure selection of independent instruments. Because APOE is highly pleiotropic and exposure effect size is hypothesized by MR not to be larger than the outcome (Steiger filtering), thus variants within ±1MB from APOE were removed in the MR‐analysis. Two tests were considered: Inverse‐Variance‐Weighted and Weighted‐Median, which allows robust MR estimates even when some invalid instruments are included.ResultAmong known AD‐GWAS genes, TREM2, PILRA, ACE, CR1, and BIN1 protein levels were associated with AD. Proteins without prior AD‐GWAS links were also found to be associated with AD including: PPBP, NRP2, AZGP2, and TNFSF13B/BAFF (Figures 1&amp;2). Interestingly, APOE and KLOTHO levels were not associated with AD (Figures 3&amp;4), though increased APOE level significantly associated with increase AD risk when including cis‐APOE variants at p &lt; 5×10−6 (Figure 5).ConclusionOur study informs the directionality of association between certain plasma protein levels and AD risk, and prioritizes candidate proteins to be considered for AD drug development.

Cardioprotective and Antifibrotic Effects of Low-Dose Renin-Angiotensin-Aldosterone System Inhibitors in Type 1 Diabetic Rat Model.

Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin-angiotensin-aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima-media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.

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.

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.

Exogenous Klotho Extends Survival in COVID-19 Model Mice.

A striking feature of COVID-19 disease is the broad spectrum of risk factors associated with case severity, as well as the diversity of clinical manifestations. While no central agent has been able to explain the pathogenesis of SARS-CoV-2 infection, the factors that most robustly correlate with severity are risk factors linked to aging. Low serum levels of Klotho, an anti-aging protein, strongly correlate with the pathogenesis of the same risk factors and manifestations of conditions similar to those expressed in severe COVID-19 cases. The current manuscript presents original research on the effects of the exogenous application of Klotho, an anti-aging protein, in COVID-19 model mice. Klotho supplementation resulted in a statistically significant survival benefit in parametric and non-parametric models. Further research is required to elucidate the mechanistic role Klotho plays in COVID-19 pathogenesis as well as the possible modulation SARS-CoV-2 may have on the biological aging process.

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.

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

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