Kuiper Lieke M, Picavet H Susan J, Rietman M Liset, Dollé Martijn E T, Verschuren W M Monique
Center for Prevention, Lifestyle and Health, National Institute for Public Health and Environment (RIVM), Bilthoven, the Netherlands.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
J Gerontol A Biol Sci Med Sci. 2025 May 5;80(6). doi: 10.1093/gerona/glae272.
Skin autofluorescence (SAF), reflecting advanced glycation endproducts' accumulation in tissue, has been proposed as a noninvasive aging biomarker. Yet, SAF has not been compared with 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 2 382 Doetinchem Cohort Study participants' (aged 46.0-85.4) cross-sectional data, of whom 1 654 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.
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，SAF尚未与成熟的基于血液的衰老生物标志物（如与衰弱相关的MetaboHealth）进行比较。此外，以前没有研究确定SAF与衰弱之间的纵向关联。我们使用了多廷赫姆队列研究中2382名参与者（年龄在46.0 - 85.4岁之间）的横断面数据，其中1654人有SAF的纵向测量数据。使用AGE Reader测量SAF。通过1H - NMR代谢组学计算MetaboHealth。采用线性回归分析SAF和MetaboHealth与36项缺陷衰弱指数之间的关联，采用逻辑回归分析根据衰弱表型确定的虚弱前期或虚弱状态。通过线性混合模型中年龄与SAF之间的交互项确定纵向关联。SAF和MetaboHealth与虚弱前期（SAF每标准差的比值比：1.21 [1.10 - 1.32]，MetaboHealth：1.35 [1.24 - 1.49]）和虚弱（SAF：1.70 [1.41 - 2.06]，MetaboHealth：1.90 [1.57 - 2.32]）的较高几率相关。相互调整后，两种衰老生物标志物仍与虚弱前期（SAF：1.16 [1.05 - 1.27]，MetaboHealth 1.33 [1.21 - 1.46]）和虚弱（SAF：1.52 [1.25 - 1.85]，MetaboHealth：1.75 [1.43 - 2.14]）相关。此外，SAF和MetaboHealth也与较高的衰弱指数得分相关（SAF每标准差的百分比增加：1.35 [1.00 - 1.70]，MetaboHealth：1.87 [1.54 - 2.20]），相互调整后也是如此（SAF：1.02 [0.68 - 1.37]，MetaboHealth：1.69 [1.35 - 2.02]）。SAF在纵向也与衰弱指数相关（每年每单位增加的百分比：0.12 [0.07 - 0.16]）。SAF和MetaboHealth的相互独立性意味着它们捕捉到了衰老过程的不同方面。总之，这些发现强调了SAF作为与年龄相关衰退生物标志物的临床潜力，与MetaboHealth联合使用时可能会进一步增强。
