Association of α-klotho and lead and cadmium: A cross-sectional study

Kim, Dong-Hoon; Lee, Sohyae; Choi, Ju-Young; Lee, Jae-Ho; Lee, Hyo‐Jung; Min, Jin‐Young; Min, Kyung Soo

doi:10.1016/j.scitotenv.2022.156938

Cited by 17 publications

(9 citation statements)

References 47 publications

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“…The Klotho gene has been regulated by epigenetic and non-epigenetic mechanisms in renal disease ( 53 ). Exposure to higher levels of environmental pollutants (e.g., lead and cadmium) is associated with elevated levels of methylation of the Klotho gene, which may alter Klotho mRNA synthesis, leading to decreased protein levels of Klotho ( 54 ). Some PFAS, such as PFOA, PFNA, PFOS, and PFHxS had the potentials to cause oxidative stress in terms of ROS generation and DNA damage and were linked to indicators of inflammation and oxidative stress ( 11 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants

Wei

et al. 2023

Front. Public Health

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PurposeExposure to perfluoroalkyl and polyfluoroalkyl substances causes oxidative stress, which is strongly associated with adverse health effects. Klotho protein plays an anti-aging role via antioxidation activity.MethodsWe investigated the levels of serum α-Klotho and PFAS exposure in adults who participated in the National Health and Nutrition Examination Survey from 2013 to 2016. A nationally representative subsample of 1,499 adults aged 40–79 years was analyzed for the associations of serum α-Klotho levels with serum PFAS exposures by correlation analysis and multiple general linear models. Of note, the potential confounding factors including age and gender were adjusted. Quantile-based g-computation models were used to assess the effects of mixed PFAS exposure on serum α-Klotho levels.ResultsThe weighted geometric mean of serum α-Klotho was 791.38 pg/mL for the subjects during 2013–2016. After adjusting for potential confounders, serum Klotho levels showed a statistically significant downward trend with increasing quartiles of PFOA and PFNA. Multivariate adjusted general linear regression analysis showed that increased exposure to PFNA was substantially associated with lower serum levels of α-Klotho, and each 1-unit increase in PFNA concentration was accompanied by a 20.23 pg/mL decrease in α-Klotho level; while no significant association was observed between other PFAS exposures and serum α-Klotho levels. It was negatively correlated between α-Klotho and Q4 for PFNA relative to the lowest quartile (Q1) of exposure (P = 0.025). It was found that the strongest negative correlation between PFNA exposure and serum α-Klotho levels was in the middle-aged (40–59 years) female participants. Furthermore, the mixture of the four PFAS substances showed an overall inverse association with serum α-Klotho concentrations, with PFNA being the major contributor.ConclusionsTaken together, in a representative sample of the U.S. middle-aged and elderly populations, serum concentrations of PFAS, especially PFNA, have been negatively associated with serum levels of α-Klotho, which is strongly associated with cognition and aging. It was important to note that the majority of associations were limited to middle-aged women. It will be meaningful to clarify the causal relationship and the pathogenic mechanisms of PFAS exposure and α-Klotho levels, which is helpful to aging and aging-related diseases.

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Section: Discussionmentioning

confidence: 99%

Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants

Wei

et al. 2023

Front. Public Health

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“…We explored the association between serum manganese and serum klotho levels after adjusting for covariates selected in accordance with the literature ( Xiao et al, 2021 ; Kim et al, 2022 ; Kresovich and Bulka, 2022 ). Sociodemographic characteristics were obtained using computer-assisted questionnaires, which included age, gender, race, educational attainment, marital status, and PIR.…”

Section: Methodsmentioning

confidence: 99%

Association between serum manganese and serum klotho in a 40–80-year-old American population from NHANES 2011–2016

et al. 2023

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Objectives: Manganese is one of the essential trace elements that are required by the human body. Klotho protein is a classic anti-aging marker. The association between the levels of serum manganese and serum klotho in individuals between the ages of 40–80 in the United States remains unclear.Methods: Data for this cross-sectional study was obtained from the National Health and Nutrition Examination Survey (NHANES 2011–2016) in the United States. We performed multiple linear regression analyses to investigate the association between the levels of serum manganese and serum klotho. Furthermore, we performed a fitted smoothing curve according to a restricted cubic spline (RCS). Stratification and subgroup analyses were performed for further verification of the results.Results: Weighted multivariate linear regression analysis showed that serum manganese levels were independently and positively associated with serum klotho levels (β = 6.30, 95% confidence interval: 3.30–9.40). Kruskal–Wallis test showed that participants with higher manganese quartiles had higher serum klotho levels (Q1: 808.54 ± 256.39 pg/mL; Q2: 854.56 ± 266.13 pg/mL; Q3: 865.13 ± 300.60 pg/mL; and Q4: 871.72 ± 338.85 pg/mL, p < 0.001). The RCS curve indicated that the association between the levels of serum manganese and serum klotho was non-linear. Furthermore, a significantly positive association was found between serum manganese and serum klotho levels in the majority of subgroups.Conclusion: A non-linear and positive association was found between the levels of serum manganese and serum klotho in individuals aged 40–80 in the United States according to the NHANES (2011–2016).

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“…This study reveals a new mediating effect of serum α-Klotho on the relationship between serum lead, mercury, and renal function. In an NHANES cross-sectional study (37) among 9800 participants aged 40-79, blood lead levels were positively associated with serum α-Klotho in US adults. Among various metals, blood lead has been linked to blood homocysteine (48), an amino acid involved in oxidative stress and aging.…”

Section: Underlying Mechanismsmentioning

confidence: 99%

“…NHANES includes interviews, physical examinations, and laboratory tests. Extensive data were collected through interviews, including demographic, socioeconomic, dietary and health-related questionnaire data (37). Laboratory tests and medical, dental and physiological examinations are performed by trained medical personnel.…”

Section: Study Populationmentioning

confidence: 99%

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Serum Protein α-Klotho Mediates the Association between Lead, Mercury, and Kidney Function

Jiang,

Guo,

Zhong

et al. 2024

Preprint

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Background Exposure to heavy metals, particularly lead and mercury, has been identified as a significant risk factor for renal dysfunction, often through mechanisms involving oxidative stress. Despite extensive research, the specific role of serum α-klotho in modulating the effects of these metals on kidney function remains unclear. This study aims to elucidate the relationship between serum levels of lead, mercury, and renal function, investigate oxidative stress's potential modulatory effects, and explore the mediating role of serum α-klotho in this context among US adults, as derived from the National Health and Nutrition Examination Survey (NHANES) data spanning 2007 to 2016. Methods In a cross-sectional analysis of 11,032 adults aged 40 to 79 years from NHANES, we measured serum lead and mercury levels via inductively coupled plasma mass spectrometry and serum α-klotho levels using enzyme-linked immunosorbent assay (ELISA). Kidney function was evaluated through the creatinine-based estimated glomerular filtration rate (eGFR). Multivariable linear regression models were applied to investigate the correlations between serum heavy metal concentrations, serum α-klotho, and eGFR. Additionally, a mediation analysis model was employed to determine the role of serum α-klotho in mediating the relationship between heavy metal exposure and renal function. Results Our findings indicate a significant association between serum lead and mercury levels and reduced eGFR, suggesting impaired renal function with increased heavy metal exposure. Mediation analysis revealed that serum α-klotho mediated 6.10–9.75% of the effect of serum lead and mercury on eGFR, highlighting its role in the pathway between heavy metal exposure and kidney function. Subgroup analysis further specified that serum α-klotho significantly mediates the relationship for lead in women and individuals aged 40–69, whereas its mediating role for mercury did not show distinct patterns across gender and age groups. Conclusions The study demonstrates that serum lead and mercury are negatively correlated with renal function, with serum α-klotho playing a mediating role in this association. These findings underscore the importance of considering serum α-klotho in the context of heavy metal exposure and kidney health, offering new insights into potential preventive and therapeutic mechanisms for renal function impairment. Further research is warranted to explore the clinical applications of targeting serum α-klotho in mitigating the adverse effects of heavy metals on the kidneys.

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Association of α-klotho and lead and cadmium: A cross-sectional study

Cited by 17 publications

References 47 publications

Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants

Association between perfluoroalkyl and polyfluoroalkyl internal exposure and serum α-Klotho levels in middle-old aged participants

Association between serum manganese and serum klotho in a 40–80-year-old American population from NHANES 2011–2016

Serum Protein α-Klotho Mediates the Association between Lead, Mercury, and Kidney Function

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