Sanchis-Gomar Fabian, Pareja-Galeano Helios, Santos-Lozano Alejandro, Garatachea Nuria, Fiuza-Luces Carmen, Venturini Letizia, Ricevuti Giovanni, Lucia Alejandro, Emanuele Enzo
Research Institute of Hospital 12 de Octubre ('i+12'), Avda. de Córdoba s/n, 28041, Madrid, Spain,
Age (Dordr). 2015 Jun;37(3):9776. doi: 10.1007/s11357-015-9776-y. Epub 2015 Apr 25.
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.
尽管全球百岁老人的数量在不断增加，但影响衰老过程的潜在因素仍仅得到部分阐释。研究人员越来越关注生物标志物，将其作为工具以更深入地了解复杂表型的病理生理学，包括实现成功衰老（即无重大慢性疾病）的能力。因此，我们开展了一项病例对照研究，调查健康百岁老人和性别匹配的健康老年对照中多种候选生物标志物的潜在关联。通过一项病例对照研究，选取了81名百岁老人（年龄≥100岁，基于他们无疾病这一事实）和46名健康老年对照（年龄70 - 80岁），测量了15种参与代谢、血管生成、炎症和骨形成调节的不同候选生物标志物的血清水平。在测试的15种生物标志物中，发现有四种分子（瑞连蛋白、胎球蛋白-A和成纤维细胞生长因子[FGF]19和21）无论性别均与成功衰老独立相关。逻辑回归分析证实，瑞连蛋白、胎球蛋白-A、FGF19和FGF21与成功衰老独立相关[预测概率(PP)=1 / [1 + 1 / exp(11.832 - 0.027×(瑞连蛋白)-0.009×(胎球蛋白-A)+0.014×(FGF19)-0.007×(FGF21)]]。四种生物标志物组合的预测概率值的曲线下面积(AUC)显示，它能够以极高的准确性区分百岁老人和老年对照(AUC>0.94，P<0.001)。尽管本质上是初步的，且受样本量小和缺乏在其他独立队列中的重复验证所限，但我们的数据表明成功衰老与血清瑞连蛋白、胎球蛋白-A、FGF19和FGF21之间存在独立关联，这可能为人类衰老过程背后的机制提供新信息。四种生物标志物组合是否可预测成功衰老值得进一步研究。
