{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:10:28Z","timestamp":1787008228311,"version":"build-2736575974"},"reference-count":42,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Rejuvenation Research"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:p>\n                    Previous studies have established associations between \u03b1-Klotho and frailty or sarcopenia; however, the causal nature of these relationships remains unclear. This study investigates the causal effects of \u03b1-Klotho on frailty and sarcopenia-related traits using Mendelian randomization (MR). Genetic instruments for circulating \u03b1-Klotho concentrations, frailty index (FI), low grip strength (LGS), appendicular lean mass (ALM), and walking pace were developed based on data from large genome-wide association studies. Two-sample MR analyses were performed, supplemented by sensitivity analyses to ensure the robustness of the findings. Reverse MR analyses were also conducted to explore potential reverse causation. The findings demonstrated an inverse causal relationship of circulating \u03b1-Klotho levels with FI (\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    = \u22120.020, 95% confidence interval [95% CI] = \u22120.036 to \u22120.004;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.017) and LGS (\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    = \u22120.033, 95% CI = \u22120.061 to \u22120.004;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    = 0.023). However, no causal relationship was observed between circulating \u03b1-Klotho levels and ALM or walking pace. Additionally, no evidence of reverse causation was identified between FI or sarcopenia-related traits and circulating \u03b1-Klotho levels. In conclusion, this MR analysis establishes an inverse causal relationship of circulating \u03b1-Klotho levels with both FI and LGS.\n                  <\/jats:p>","DOI":"10.1089\/rej.2024.0057","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T11:43:16Z","timestamp":1738582996000},"page":"146-155","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Relationship of \u03b1-Klotho with Frailty Index and Sarcopenia: A Bidirectional Mendelian Randomization Study"],"prefix":"10.1177","volume":"28","author":[{"given":"Yue","family":"Zhu","sequence":"first","affiliation":[{"name":"Division of Life Sciences and Medicine, Hefei Ion Medical Center, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Jun","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanjing Gaochun People\u2019s Hospital, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The People\u2019s Hospital of Huangshan, Huangshan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-3806","authenticated-orcid":false,"given":"Rui","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Hefei Ion Medical Center, the First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31785-4"},{"key":"e_1_3_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101498"},{"key":"e_1_3_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1926"},{"key":"e_1_3_8_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afac064"},{"key":"e_1_3_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2022.10.007"},{"key":"e_1_3_8_7_2","article-title":"Epidemiology of sarcopenia: Prevalence, risk factors, and consequences","volume":"144","author":"Yuan S","year":"2023","unstructured":"Yuan S, , Larsson SC. Epidemiology of sarcopenia: Prevalence, risk factors, and consequences. Metabolism, 2023; 144:155533.","journal-title":"Metabolism"},{"key":"e_1_3_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12783"},{"key":"e_1_3_8_9_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2013-1079"},{"key":"e_1_3_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2008.10.002"},{"key":"e_1_3_8_11_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02840320"},{"key":"e_1_3_8_12_2","article-title":"The controversy of klotho as a potential biomarker in chronic kidney disease","volume":"13","author":"Yu LX","year":"2022","unstructured":"Yu LX, , Li SS, , Sha MY, et al. The controversy of klotho as a potential biomarker in chronic kidney disease. 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Association between uric acid and risk of venous thromboembolism in East Asian populations: A cohort and Mendelian randomization study. 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