Determination of the reference interval for urinary klotho to creatinine ratio of healthy dogs.

For several years, alpha klotho has been considered as a candidate biomarker in chronic kidney disease (CKD), progression of CKD and CKD mineral bone disorders (CKD-MBD). The evidence on the relationship between klotho and kidney function is controversial in some areas. The aim of the study was to identify the influence of age, sex and breed on urinary alpha klotho, values in the early stages of CKD within the studied population and determine a reference interval in a group of healthy dogs. Significantly higher values were measured in older dogs over 6 years old (p = 0.026, p = 0.0007) and in the breed German Shepherd than Belgian Shepherd (p = 0.0401). On the basis of sex and in small breed dogs, no significant differences were noted. In dogs with CKD stage 2, alpha klotho values were significantly lower (p = 0.0135) than in healthy dogs. Within the studied population, a reference interval for urinary klotho to creatinine ratio (UrKl/Cr) was determined in the range of 3.94-23.55 pg/gCr. Since our findings show that alpha klotho is associated with older age, we assume that this may have influenced the results in the group of dogs with CKD stage 1 due to the presence of predominantly old dogs in this group. Future studies would be needed to consider age as a factor affecting urinary alpha klotho in dogs with CKD.

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

AIMS: To investigate the potential linear relationship between serum concentrations of klotho and frailty. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Corrigendum: Fucoidan ameliorates renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats by targeting FGF23-Klotho signaling axis.

[This corrects the article DOI: 10.3389/fphar.2020.586725.].

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

Purpose: 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. Patients and methods: 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. Results: 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. Conclusion: 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.

Biohybrid hydrogel inhibiting ß-klotho/HDAC3 axis for hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC), ranking as the fourth most prevalent cancer globally, has garnered significant attention due to its high invasiveness and mortality rates. However, drug therapies face challenges of inadequate efficacy and unclear mechanisms. Here, we propose a novel biohybrid hydrogel that targets ß-Klotho (KLB) for HCC treatment. As a dual-network hydrogel, this gel combines gelatin methacryloyl (GelMA) and polyvinyl alcohol (PVA) to ensure biocompatibility while enhancing controlled drug release. Notably, it exhibits good storage stability, high drug load capacity, and efficient water absorption. By introducing the HDAC3 inhibitor RGFP966, we can selectively inhibit the activation of ß-Klotho. This deactivation effectively blocks the FGF21-KLB signaling pathway and inhibits the progression of HCC. Importantly, we have successfully validated this unique phenomenon both in vivo and in vitro, providing substantial evidence for the efficacy of this hydrogel-based anti-tumor drug delivery system as a promising strategy for HCC treatment. This innovative research outcome brings new hope to the field of tumor therapy, providing a reliable theoretical foundation for future clinical applications.

Correlation of serum Klotho, fetuin-A, and MGP levels with coronary artery calcification in maintenance hemodialysis patients.

OBJECTIVE: This study was to investigate the role of serum Klotho, fetuin-A, and Matrix Gla Protein (MGP) in Coronary Artery Calcification (CAC) in patients with Maintenance Hemodialysis (MHD) and their predictive value for CAC. METHODS: 100 patients receiving MHD were selected. Serum Klotho, fetuin-A, and MGP levels were detected by ELISA. CAC scores were assessed by coronary CT scan. Multifactor analysis was used to evaluate the risk factors affecting CAC. The ability of serum Klotho, fetuin-A, and MGP levels to diagnose CAC was evaluated by receiver operating characteristic curves. RESULTS: Serum Klotho, fetuin-A, and MGP were independent risk factors for CAC. Serum Klotho, fetuin-A, and MGP were valuable in the diagnosis of CAC in MHD patients. CONCLUSION: There is a close relationship between Klotho, fetuin-A, and MGP levels in MHD patients and CAC.

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.

BACKGROUND: This study aimed to explore the potential associations between trans fatty acid (TFA) and α-klotho levels. METHODS: Datasets 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. RESULTS: A 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 ß 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. CONCLUSIONS: L-shaped correlations between plasma PA, VA, EA, and total TFA levels and serum α-klotho levels were observed among adults in the United States.

The association of platelet count, high-density lipoprotein cholesterol, and platelet/high-density lipoprotein cholesterol ratio with serum soluble Klotho.

BACKGROUND AND OBJECTIVE: Klotho is a protein that is closely related to human aging. Soluble Klotho (S-Klotho) is a circulating protein, and its level decreases in response to systemic inflammation. The relationship between the platelet/high-density lipoprotein cholesterol ratio (PHR), an emerging inflammatory index, and S-Klotho concentrations is still unclear. In addition, the mean platelet volume has been confirmed to have a significant negative association with S-Klotho concentrations, but the relationship between the platelet count (PC) and S-Klotho concentrations has not yet been reported. METHODS: Data from individuals who participated in the National Health and Nutrition Examination Survey (NHANES) during the five cycles from 2007 to 2016 were retrieved for analysis. Linear regression, two-piecewise linear regression, and restricted cubic spline (RCS) methods were used to analyze the associations of the PHR index and its components with S-Klotho concentrations. In addition, subgroup analysis and effect modification tests were conducted. RESULTS: A total of 11,123 participants (5463 men (48.17%)), with an average age of 56.2 years, were included. After full adjustment, the S-Klotho levels of participants in the highest quartile group of PHR (ß: -51.19, 95% CI: -75.41 to -26.97, P < 0.001) and the highest quartile group of PC (ß: -72.34, 95% CI: -93.32 to -51.37, P < 0.0001) were significantly lower than those in their respective lowest quartile groups, and a significant downward trend was presented among the four groups (P for trend < 0.05, respectively). However, high-density lipoprotein cholesterol (HDL-C) concentrations were not significantly associated with S-Klotho concentrations. RCS revealed that the PHR and PC were nonlinearly associated with S-Klotho concentrations; two-piecewise linear regression revealed that the inflection points were 175.269 and 152, respectively, and that these associations slightly weakened after the inflection point. According to the subgroup analysis, liver disease status enhanced the association between the PC and S-Klotho concentrations. CONCLUSIONS: Both the PHR and PC were significantly negatively associated with S-Klotho concentrations, and these associations were nonlinear. There was no significant association between HDL-C and S-Klotho concentrations. Liver disease status enhances the negative association between the PC and S-Klotho concentrations, and the specific mechanism deserves further exploration.

Fibroblast growth-factor 23-Klotho axis is associated with systemic inflammation and myokine profile in children with chronic kidney disease.

BACKGROUND: Chronic kidney disease is linked to a disturbed fibroblast growth factor-23 (FGF23)-Klotho axis and an imbalance between myostatin and insulin-like growth factor-1 (IGF-1) expression. This cross-sectional study investigates the association of the FGF23-Klotho axis and myokine profile with serum interleukin-6 (IL-6) and their interactions in pediatric patients. METHODS: Serum calcium, phosphorus, 25-hydroxyvitamin D, parathormone, c-terminal FGF23, a-Klotho, myostatin, follistatin, IGF-1, and IL-6 were measured in 53 patients with GFR < 60 ml/min/1,73m2. Myostatin to lean mass (LM) and to IGF-1 ratios were calculated. IL-6 level > 3rd quartile was considered as high. RESULTS: Myostatin, IGF-1, and follistatin were correlated to LM (rs = 0.513, p < 0.001, rs = 0.652, p < 0.001, rs=-0.483, p < 0.001). Myostatin and follistatin were correlated to IGF-1 (rs = 0.340, p = 0.014, rs=-0.385, p = 0.005). Myostatin/LM but not myostatin or myostatin/IGF-1 ratio was significantly higher in CKD 5D patients (p = 0.001,p = 0.844, p = 0.111). Among mineral bone parameters, lnFGF23 was correlated to lnIL-6 (rs = 0.397, p = 0.004) and associated with high IL-6 (OR 1.905, 95% CI 1.023-3.548). Among myokines, myostatin/IGF-1 ratio was correlated to lnIL-6 (rs = 0.395, p = 0.004) and associated with high IL-6 (OR 1.113, 95% CI 1.028-1.205). All associations were adjusted to CKD stage. Myostatin was correlated to lnFGF23 (rs = 0.331, p = 0.025) and myostatin/IGF-1 ratio to lnKlotho (rs=-0.363, p = 0.013), after adjustment for CKD stage, lnIL-6 and other mineral bone parameters. CONCLUSIONS: In pediatric CKD, FGF23 and myostatin/IGF-1 ratio are associated with IL-6, indicating a link between systemic inflammation, mineral bone, and myokine disorders. The correlations between myostatin and FGF23 and between myostatin/IGF-1 and Klotho suggest an interaction between mineral bone and muscle metabolism.

Association between the triglyceride-glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007-2016.

Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed to explore the relationship between the triglyceride-glucose (TyG) index (a simple marker of insulin resistance) and serum soluble Klotho (S-Klotho) levels. The cross-sectional study comprised 5237 adults aged 40-79 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The serum levels of S-Klotho were measured by enzyme-linked immunosorbent assay. The association between the TyG index and S-Klotho levels was investigated by multiple linear regression models, smoothed curve fitting, segmented linear regression models, subgroup analyses, and interaction tests. The TyG index was inversely associated with serum S-Klotho level after full adjustment (ß = - 45.11, 95% CI (- 79.53, - 10.69), P = 0.011). Furthermore, we also found a non-linear correlation and saturation phenomenon between the TyG index and serum S-Klotho levels, with a turning point of 9.56. In addition, a significant interaction effect of sex was found between the two (P for interaction < 0.001), with a more pronounced association observed in females. Further studies are required to explore the mechanisms and verify the correlation.

Relationship between uric acid to high-density cholesterol ratio (UHR) and circulating α-klotho: evidence from NHANES 2007-2016.

OBJECTIVE: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. METHODS: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. RESULTS: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. CONCLUSION: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.

Systemic immunoinflammatory indexes in albuminuric adults are negatively associated with α-klotho: evidence from NHANES 2007-2016.

BACKGROUND: Systemic Immune-Inflammation Index (SII) is a novel inflammatory biomarker closely associated with the inflammatory response and chronic kidney disease. Klotho is implicated as a pathogenic factor in the progression of kidney disease, and supplementation of Klotho may delay the progression of chronic kidney disease by inhibiting the inflammatory response. Our aim is to investigate the potential relationship between SII and Klotho in adult patients in the United States and explore the differences in the populations with and without albuminuria. METHODS: We conducted a cross-sectional study recruiting adult participants with complete data on SII, Klotho, and urine albumin-to-creatinine ratio (ACR) from the National Health and Nutrition Examination Survey from 2007 to 2016. SII was calculated as platelet count × neutrophil count/lymphocyte count, with abnormal elevation defined as values exceeding 330 × 10^9/L. Albuminuria was defined as ACR >30 mg/g. Weighted multivariable regression analysis and subgroup analysis were employed to explore the independent relationship between SII and Klotho. RESULTS: Our study included a total of 10,592 individuals. In all populations, non-albuminuria population, and proteinuria population with ACR ≥ 30, participants with abnormally elevated SII levels, as compared to those with SII less than 330 × 10^9/L, showed a negative correlation between elevated SII levels and increased Klotho, which persisted after adjusting for covariates. CONCLUSIONS: There is a negative correlation between SII and Klotho in adult patients in the United States. This finding complements previous research but requires further analysis through large prospective studies.

Klotho: molecular mechanisms and emerging therapeutics in central nervous system diseases.

Klotho is recognized as an aging-suppressor protein that is implicated in a variety of processes and signaling pathways. The anti-inflammatory, anti-apoptotic, anti-oxidant, and anti-tumor bioactivities of klotho have extended its application in neurosciences and made the protein popular for its lifespan-extending capacity. Furthermore, it has been demonstrated that klotho levels would reduce with aging and numerous pathologies, particularly those related to the central nervous system (CNS). Evidence supports the idea that klotho can be a key therapeutic target in CNS diseases such as amyotrophic lateral sclerosis, Parkinson's disease, stroke, and Alzheimer's disease. Reviewing the literature suggests that the upregulation of klotho expression regulates various signaling pathways related to autophagy, oxidative stress, inflammation, cognition, and ferroptosis in neurological disorders. Therefore, it has been of great interest to develop drugs or agents that boost or restore klotho levels. In this regard, the present review was designed and aimed to gather the delegated documents regarding the therapeutic potential of Klotho in CNS diseases focusing on the molecular and cellular mechanisms.

Apolipoproteine and KLOTHO Gene Variants Do Not Affect the Penetrance of Fragile X-Associated Tremor/Ataxia Syndrome.

In this study, the potential role and interaction of the APOε and KLOTHO genes on the penetrance of fragile X-associated tremor/ataxia syndrome (FXTAS) and on the IQ trajectory were investigated. FXTAS was diagnosed based on molecular, clinical and radiological criteria. Males with the premutation (PM) over 50 years, 165 with and 34 without an FXTAS diagnosis, were included in this study and were compared based on their APO (ε2-ε3-ε4) and KLOTHO variant (KL-VS) genotypes. The effect of APOε4 on FXTAS stage and on diagnosis did not differ significantly by KL-VS genotype with interaction effect p = 0.662 and p = 0.91, respectively. In the FXTAS individuals with an APOε2 allele, a marginal significance was observed towards a larger decline in verbal IQ (VIQ) in individuals with an APOε4 allele compared to those without an APOε4 allele (p = 0.071). In conclusion, our findings suggest that the APOε4 and KL-VS genotypes alone or through their interaction effect do not appear to predispose to either FXTAS diagnosis or stage in male carriers of the PM allele. A further study is needed to establish the trend of IQ decline in the FXTAS individuals who carry APOε4 with APOε2 compared to those without APOε4.

Sex-dependent changes in AMPAR expression and Na, K-ATPase activity in the cerebellum and hippocampus of α-Klotho-Hypomorphic mice.

Aging is characterized by a functional decline in several physiological systems. α-Klotho-hypomorphic mice (Kl-/-) exhibit accelerated aging and cognitive decline. We evaluated whether male and female α-Klotho-hypomorphic mice show changes in the expression of synaptic proteins, N-methyl-d-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits, postsynaptic density protein 95 (PSD-95), synaptophysin and synapsin, and the activity of Na+, K+-ATPase (NaK) isoforms in the cerebellum and hippocampus. In this study, we demonstrated that in the cerebellum, Kl-/- male mice have reduced expression of GluA1 (AMPA) compared to wild-type (Kl+/+) males and Kl-/- females. Also, Kl-/- male and female mice show reduced ɑ2/ɑ3-NaK and Mg2+-ATPase activities in the cerebellum, respectively, and sex-based differences in NaK and Mg2+-ATPase activities in both the regions. Our findings suggest that α-Klotho could influence the expression of AMPAR and the activity of NaK isoforms in the cerebellum in a sex-dependent manner, and these changes may contribute, in part, to cognitive decline.

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.

Dietary folate intake and serum klotho levels in adults aged 40-79 years: a cross-sectional study from the national health and nutrition examination survey 2007-2016.

Objective: This study aims to explore the relationship between dietary folate intake and serum Klotho levels in adults from aged 40 to 79 years in the United States, seeking to elucidate the intricacies of their interaction. Methods: Analyzing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2016. The survey research determined folate intake through a 24-h dietary recall and nutrient density modeling, and assessed Klotho levels using enzyme-linked immunosorbent assay (ELISA). The relationship between folate intake and Klotho levels was evaluated using weighted linear regression, and complemented by analysis via smoothed curve models for nuanced understanding. Results: The study encompassed 10,278 participants, with an average age of 57.64 years, revealing a noteworthy positive correlation between dietary folate and serum Klotho levels. The regression coefficient stood at 0.11 (95% confidence interval, 0.05, 0.18) post-adjustment for various covariates. When dietary folate intake was categorized into quartiles, the second, third, and fourth quartiles exhibited statistically significant differences compared to the lowest quartile. This indicates that higher folate intake correlates with increased serum Klotho levels. These findings underscore the potential benefits of elevating folate intake to enhance serum Klotho levels. Stratified analysis indicated that this association was more pronounced among males aged 60 years or older and individuals with hypertension. Conclusion: The findings suggest a significant correlation between increased dietary folate intake and elevated serum Klotho levels in adults aged 40-79 years. Hinting at the potential nutritional influences on the aging process and associated health conditions. This calls for further exploration into the mechanisms and broader implications of this association.

Association of Klotho with Neuropsychiatric Disorder: A Meta-Analysis.

Neuropsychiatric disorders are mainly concerned with the behavioural, emotional and cognition symptoms that may be due to disturbed cerebral functions or extracerebral disease. Klotho protein is an antiaging protein that is mostly associated with cognitive changes in these disorders and thus this meta-analysis is conducted in order to find Klotho proteins association with these disorders. We searched related topics in pubmed, by using the key word i.e. Klotho and related disorder from neuropsychiatry e.g. Klotho levels and schizophrenia, Klotho levels and parkinsonism etc. Total 82 studies were found till 9th February 2021 after extensive search and 10 studies were selected for further analysis. The meta-analysis of studies was performed using the Random effect model. The forest plot represented each study in the meta-analysis, so as to make the comparison of SMD value across studies. The meta-analysis outcome demonstrated that overall schizophrenia had higher klotho levels as compared with bipolar disorder, psychosocial stress, parkinsonism, multiple sclerosis, depression, Alzheimer's disease, and healthy controls, followed by MS. The meta-analysis also found that bipolar disorder and Alzheimer's disease were associated with low klotho levels as compared to schizophrenia. The results indicate a significant association of the klotho levels and schizophrenia. Further studies are needed to characterize the potential biological roles of klotho levels in psychiatric disorders.