Skin autofluorescence (SAF), reflecting advanced glycation end-products’ accumulation in tissue, has been proposed as a non-invasive aging biomarker. Yet, SAF has not been compared to well-established blood-based aging biomarkers such as MetaboHealth in association with frailty. Furthermore, no previous study determined the longitudinal association of SAF with frailty. We used 2382 Doetinchem Cohort Study participants’ (aged 46.0 to 85.4) cross-sectional data, of whom 1654 had longitudinal SAF measurements. SAF was measured using the AGE reader™. MetaboHealth was calculated on 1H-NMR-metabolomics. Linear regressions were used for the associations of SAF and MetaboHealth on the 36-deficit frailty index and logistic regressions for being pre-frail or frail as determined by the frailty phenotype. Longitudinal associations were determined by an interaction term between age and SAF in a linear mixed model. SAF and MetaboHealth were associated with higher odds of pre-frailty (odd ratios per standard deviation SAF: 1.21(1.10;1.32), MetaboHealth: 1.35(1.24;1.49)) and frailty (SAF: 1.70(1.41;2.06), MetaboHealth: 1.90(1.57;2.32)). When mutually adjusted, both aging biomarkers remained associated with pre-frailty (SAF: 1.16(1.05;1.27), MetaboHealth 1.33(1.21;1.46)) and frailty (SAF: 1.52(1.25;1.85), MetaboHealth: 1.75(1.43;2.14)). Additionally, SAF and MetaboHealth were associated with higher frailty index scores (percentage increase per standard deviation SAF:1.35(1.00;1.70), MetaboHealth: 1.87(1.54;2.20)), also after mutual adjustment (SAF: 1.02(0.68;1.37), MetaboHealth: 1.69(1.35;2.02)). SAF was also longitudinally associated with the frailty index (percentage per unit/year increase 0.12(0.07;0.16)). The mutual independence of SAF and MetaboHealth implies they capture distinct aspects of the aging process. Altogether, these findings emphasize SAF’s clinical potential as an age-related decline biomarker, which could be further enhanced when combined with MetaboHealth.

中文翻译：

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晚期糖基化终末产物和代谢组学与虚弱独立相关：纵向 Doetinchem 队列研究


皮肤自发荧光 （SAF） 反映了晚期糖基化终产物在组织中的积累，已被提议作为一种非侵入性衰老生物标志物。然而，尚未将 SAF 与公认的基于血液的衰老生物标志物（如 MetaboHealth）与虚弱相关进行比较。此外，以前的研究没有确定 SAF 与虚弱的纵向关联。我们使用了 2382 名 Doetinchem 队列研究参与者 （年龄 46.0 至 85.4） 的横断面数据，其中 1654 名进行了纵向 SAF 测量。使用 AGE 读数仪™测量 SAF。MetaboHealth 是根据 1H-NMR-代谢组学计算的。线性回归用于 SAF 和 MetaboHealth 在 36 缺陷衰弱指数上的关联，以及由衰弱表型确定的虚弱前期或虚弱的 logistic 回归。纵向关联由线性混合模型中年龄和 SAF 之间的交互项确定。SAF 和 MetaboHealth 与较高的衰弱前期几率相关（每个标准差 SAF 的比值比：1.21（1.10;1.32），代谢健康：1.35（1.24;1.49）） 和虚弱 （SAF： 1.70（1.41;2.06），代谢健康：1.90（1.57;当相互调整时，两种衰老生物标志物仍然与衰弱前期相关 （SAF： 1.16（1.05;1.27）、MetaboHealth 1.33（1.21;1.46）） 和虚弱 （SAF： 1.52（1.25;1.85），代谢健康：1.75（1.43;2.14））。此外，SAF 和 MetaboHealth 与较高的虚弱指数评分相关（每个标准差 SAF 的百分比增加：1.35（1.00;1.70），代谢健康：1.87（1.54;2.20）），也是在相互调整后（SAF：1.02（0.68;1.37），代谢健康：1.69（1.35;SAF 也与衰弱指数纵向相关（每单位/年百分比增加 0.12（0.07;0.16)). SAF 和 MetaboHealth 的相互独立性意味着它们捕捉了衰老过程的不同方面。总而言之，这些发现强调了 SAF 作为与年龄相关的衰退生物标志物的临床潜力，当与 MetaboHealth 结合使用时，可以进一步增强。