Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study
Purpose: This study aimed to explore the association and causal links between sex steroid hormones and the anti-aging protein α-Klotho, extending to investigate the mediation effects of potential mediators. Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 201...
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Elsevier
2025-03-01
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| Series: | Experimental Gerontology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0531556525000270 |
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| author | Andong Guo Pengcheng Chen Jishuang Cao Chenrui Wu Sentai Ding |
| author_facet | Andong Guo Pengcheng Chen Jishuang Cao Chenrui Wu Sentai Ding |
| author_sort | Andong Guo |
| collection | DOAJ |
| description | Purpose: This study aimed to explore the association and causal links between sex steroid hormones and the anti-aging protein α-Klotho, extending to investigate the mediation effects of potential mediators. Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016, this study performed weighted multivariable-adjusted logistic regression to evaluate the association between sex steroid hormones and α-Klotho. Then, utilizing summary data from genome-wide association studies (GWAS), a bidirectional two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between sex steroid hormones and α-Klotho. Finally, mediation analysis was conducted to delineate the influence of five identified potential mediators on the sex steroid hormones-α-Klotho association. Results: In men, significant positive correlations with α-Klotho were consistent across both unadjusted and fully adjusted models for total testosterone (TT), bio-available testosterone (Bio-T), estradiol (E2) and sex hormone-binding globulin (SHBG) (Model 3: TT: β = 3.54, 95 % CI: 1.63–5.44, P = 0.0003; Bio-T: β = 1.74, 95 % CI: 0.73–2.74, P = 0.0007; E2: β = 0.25, 95 % CI: 0.11–0.38, P = 0.0003; SHBG: β = 0.95, 95 % CI: 0.63–1.27, P < 0.0001); In premenopausal women, we detected a potential nonlinear relationship between TT levels and α-Klotho, with α-Klotho levels rising to a peak at a TT level of 72.2 ng/mL, after which they declined. Furthermore, results from MR analyses reaffirmed positive associations of TT and Bio-T with α-Klotho in men (TT: β = 3.54, 95 % CI: 1.63–5.44, P = 0.0003; Bio-T: β = 1.74, 95 % CI: 0.73–2.74, P = 0.0007). Finally, significant mediation effects were observed for uric acid (β = 0.27, 95 % CI: 0.15–0.67, P < 0.0001) and creatinine (β = 0.05, 95 % CI: 0.01–0.16, P = 0.0060), accounting for 26.7 % and 5.23 % of the total mediation effect, respectively. Conclusion: In conclusion, our results demonstrate that both TT and Bio-T enhance the expression of α-Klotho in men. The positive association observed may be partly mediated by uric acid and creatinine. |
| format | Article |
| id | doaj-art-b9d011acbd4446d090d2e019e6382271 |
| institution | Kabale University |
| issn | 1873-6815 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Experimental Gerontology |
| spelling | doaj-art-b9d011acbd4446d090d2e019e63822712025-02-05T04:31:07ZengElsevierExperimental Gerontology1873-68152025-03-01201112699Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization studyAndong Guo0Pengcheng Chen1Jishuang Cao2Chenrui Wu3Sentai Ding4Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, ChinaDepartment of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, ChinaDepartment of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, ChinaDepartment of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Corresponding author at: Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China.Purpose: This study aimed to explore the association and causal links between sex steroid hormones and the anti-aging protein α-Klotho, extending to investigate the mediation effects of potential mediators. Methods: Based on data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016, this study performed weighted multivariable-adjusted logistic regression to evaluate the association between sex steroid hormones and α-Klotho. Then, utilizing summary data from genome-wide association studies (GWAS), a bidirectional two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between sex steroid hormones and α-Klotho. Finally, mediation analysis was conducted to delineate the influence of five identified potential mediators on the sex steroid hormones-α-Klotho association. Results: In men, significant positive correlations with α-Klotho were consistent across both unadjusted and fully adjusted models for total testosterone (TT), bio-available testosterone (Bio-T), estradiol (E2) and sex hormone-binding globulin (SHBG) (Model 3: TT: β = 3.54, 95 % CI: 1.63–5.44, P = 0.0003; Bio-T: β = 1.74, 95 % CI: 0.73–2.74, P = 0.0007; E2: β = 0.25, 95 % CI: 0.11–0.38, P = 0.0003; SHBG: β = 0.95, 95 % CI: 0.63–1.27, P < 0.0001); In premenopausal women, we detected a potential nonlinear relationship between TT levels and α-Klotho, with α-Klotho levels rising to a peak at a TT level of 72.2 ng/mL, after which they declined. Furthermore, results from MR analyses reaffirmed positive associations of TT and Bio-T with α-Klotho in men (TT: β = 3.54, 95 % CI: 1.63–5.44, P = 0.0003; Bio-T: β = 1.74, 95 % CI: 0.73–2.74, P = 0.0007). Finally, significant mediation effects were observed for uric acid (β = 0.27, 95 % CI: 0.15–0.67, P < 0.0001) and creatinine (β = 0.05, 95 % CI: 0.01–0.16, P = 0.0060), accounting for 26.7 % and 5.23 % of the total mediation effect, respectively. Conclusion: In conclusion, our results demonstrate that both TT and Bio-T enhance the expression of α-Klotho in men. The positive association observed may be partly mediated by uric acid and creatinine.http://www.sciencedirect.com/science/article/pii/S0531556525000270α-KlothoSex steroid hormonesMediation analysisNHANESMendelian randomization |
| spellingShingle | Andong Guo Pengcheng Chen Jishuang Cao Chenrui Wu Sentai Ding Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study Experimental Gerontology α-Klotho Sex steroid hormones Mediation analysis NHANES Mendelian randomization |
| title | Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study |
| title_full | Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study |
| title_fullStr | Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study |
| title_full_unstemmed | Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study |
| title_short | Association between sex steroid hormones and α-klotho: Results from the NHANES 2013-2016 and Mendelian randomization study |
| title_sort | association between sex steroid hormones and α klotho results from the nhanes 2013 2016 and mendelian randomization study |
| topic | α-Klotho Sex steroid hormones Mediation analysis NHANES Mendelian randomization |
| url | http://www.sciencedirect.com/science/article/pii/S0531556525000270 |
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