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DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample\u2010based methylation changes of skeletal muscle function\u2010related factors in patients with sarcopenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The overall DNA methylation levels were analysed by using MethlTarget\u2122 DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged \u226565\u00a0years) and 50 age\u2010 and sex\u2010matched non\u2010sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation\u2010specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut\u2010off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 1149 cytosine\u2010phosphate\u2010guanine (CpG) sites of 27 skeletal muscle function\u2010related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation\u2010specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.372, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), grip strength (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.334, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and gait speed (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.411, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). ROC curve analysis indicated that the optimal cut\u2010off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC\u00a0=\u00a00.807, 95% CI\u00a0=\u00a00.756\u20130.858, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (&lt;0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR\u00a0=\u00a09.223, 95% CI: 6.614\u201312.861, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13472","type":"journal-article","created":{"date-parts":[[2024,4,20]],"date-time":"2024-04-20T08:03:51Z","timestamp":1713600231000},"page":"1209-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["DNA methylation of skeletal muscle function\u2010related secretary factors identifies FGF2 as a potential biomarker for sarcopenia"],"prefix":"10.1002","volume":"15","author":[{"given":"Jia\u2010Wen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Zhongda Hospital, School of Medicine Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng\u2010Kai","family":"Shen","sequence":"additional","affiliation":[{"name":"Jiangsu Province Center for Disease Control and Prevention  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Shuang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei\u2010Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Xian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Sir Run Run Hospital Nanjing Medical University  Nanjing 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