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A preliminary candidate approach identifies the combination of chemerin fetuin-A and fibroblast growth factors 19 and 21 as a potential biomarker panel of successful aging

机译:初步的候选方法将凯莫瑞胎球蛋白A和成纤维细胞生长因子19和21的组合确定为成功衰老的潜在生物标志物

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摘要

Although the number of centenarians is growing worldwide, the potential factors influencing the aging process remain only partially elucidated. Researchers are increasingly focusing toward biomarkers as tools to shed more light on the pathophysiology of complex phenotypes, including the ability to reach successful aging, i.e., free of major chronic diseases. We therefore conducted a case-control study examining the potential associations of multiple candidate biomarkers in healthy centenarians and sex-matched healthy elderly controls. Using a case-control study of 81 centenarians (aged ≥ 100 years) selected based on the fact that they were disease-free and 46 healthy elderly controls (aged 70–80 years), serum levels of 15 different candidate biomarkers involved in the regulation of metabolism, angiogenesis, inflammation, and bone formation were measured. Of the 15 biomarkers tested, four molecules (chemerin, fetuin-A, and fibroblast growth factors [FGF] 19 and 21) were found to be independently associated with successful aging regardless of sex. Logistic regression analysis confirmed that chemerin, fetuin-A, FGF19, and FGF21 were independently associated with successful aging [predicted probability (PP) = 1 / [1 + 1 / exp (11.832 − 0.027 × (chemerin) − 0.009 × (fetuin-A) + 0.014 × (FGF19) − 0.007 × (FGF21)]. The area under the curve (AUC) of predicted probability values for the four-biomarker panel revealed that it can discriminate between centenarians and elderly controls with excellent accuracy (AUC > 0.94, P < 0.001). Although preliminary in essence and limited by the low sample size and lack of replication in other independent cohorts, our data suggest an independent association between successful aging and serum chemerin, fetuin-A, FGF19, and FGF21, which may provide novel information on the mechanisms behind the human aging process. Whether the four-biomarker panel may predict successful aging deserves further scrutiny.Electronic supplementary materialThe online version of this article (doi:10.1007/s11357-015-9776-y) contains supplementary material, which is available to authorized users.
机译:尽管全世界百岁老人的数量在增长,但影响衰老过程的潜在因素仍只是部分阐明。研究人员越来越关注生物标记物,将其作为揭示复杂表型病理生理的工具,包括达到成功衰老的能力,即没有重大慢性疾病。因此,我们进行了一项病例对照研究,研究了健康百岁老人和性别匹配的健康老年人对照中多种候选生物标志物的潜在关联。基于对81位百岁老人(无病年龄≥100岁)的选择,基于他们无病的事实和46位健康的老年对照组(年龄70-80岁)的病例对照研究,该法规涉及15种不同的候选生物标志物的血清水平测量新陈代谢,血管生成,炎症和骨形成情况。在测试的15种生物标志物中,发现4个分子(chemerin,fetuin-A和成纤维细胞生长因子[FGF] 19和21)与成功的衰老无关,而与性别无关。 Logistic回归分析证实chemerin,fetuin-A,FGF19和FGF21与成功的衰老独立相关[预测概率(PP)= 1 / [1 + 1 / exp(11.832-0.027×(chemerin)-0.009×(fetuin- A)+ 0.014×(FGF19)-0.007×(FGF21)]。四个生物标志物面板的预测概率值的曲线下面积(AUC)显示,它可以区分百岁老人和老年人,且准确性极高(AUC> 0.94,P <0.001)。尽管从本质上说是初步的,并且受其他独立队列中样本量少和缺乏复制的限制,但我们的数据表明成功的衰老与血清凯莫瑞,胎球蛋白-A,FGF19和FGF21之间存在独立的关联,可能会提供有关人类衰老过程背后机制的新颖信息。四个生物标志物小组是否可以预测成功的衰老值得进一步审查。电子补充材料本文的在线版本(doi:10.1007 / s11357-015-9776-y)拥有补充材料,授权用户可以使用。

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