Skin Autofluorescence, a Noninvasive Biomarker of Advanced Glycation End-products, Is Associated With Frailty: The Rotterdam Study

Abstract Background Accumulation of advanced glycation end-products (AGEs) in tissues has been linked to various age-related disease phenotypes. Therefore, we investigated the potential relationship between skin AGE accumulation and frailty. Methods A cross-sectional analysis was performed on 2 521 participants from the Rotterdam Study. Skin AGEs were assessed as skin autofluorescence (SAF) using the AGE reader™. We used 2 approaches to define frailty. Fried's criteria, including weight loss, weakness, slow gait speed, exhaustion, and low physical activity, were used to define physical frailty (presence of ≥3 components) and prefrailty (presence of ≤2 components). Rockwood's concept, including 38 deficits from physical and psychosocial health domains, was used to calculate the frailty index (score 0–1). Multinomial logistic and multivariate linear regression were used with SAF as exposure and physical frailty (ordinal) and frailty index (continuous) as outcome adjusting for age, sex, diabetes, renal function, socioeconomic status, and smoking status. Results The mean SAF was 2.39 ± 0.49 arbitrary units and the median age was 74.2 (14.0) years. Regarding physical frailty, 96 persons (4%) were frail and 1 221 (48%) were prefrail. Skin autofluorescence was associated with both being prefrail (odds ratio [95% confidence interval] = 1.29 [1.07–1.56]) and frail (1.87 [1.20–2.90]) compared with nonfrail. Regarding the frailty index, the median value was 0.14 (0.10–0.19) and higher SAF was also associated with a higher frailty index (coefficient, B = 0.017 (0.011–0.023]). Conclusions Higher skin AGEs are associated with both physical frailty and frailty index. Longitudinal studies are needed to evaluate the causality and the potential of SAF as a biomarker to screen frailty.