Dataset Information

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.

SUBMITTER: Waqas K

PROVIDER: S-EPMC9536452 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Waqas Komal K Chen Jinluan J Rivadeneira Fernando F Uitterlinden André G AG Voortman Trudy T Zillikens M Carola MC

The journals of gerontology. Series A, Biological sciences and medical sciences 20221001 10

<h4>Background</h4>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.<h4>Methods</h4>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 lo ...[more]

PMID: 35099530

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Project description:Advanced glycation end-products (AGEs), which bind to type 1 collagen in bone and skin, have been implicated in reduced bone quality. The AGE reader™ measures skin autofluorescence (SAF), which might be regarded as a marker of long-term accumulation of AGEs in tissues. We investigated the association of SAF with bone mineral density (BMD) and fractures in the general population. We studied 2853 individuals from the Rotterdam Study with available SAF measurements (median age, 74.1 years) and with data on prevalent major osteoporotic (MOFs: hip, humerus, wrist, clinical vertebral) and vertebral fractures (VFs: clinical + radiographic Genant's grade 2 and 3). Radiographs were assessed 4 to 5 years before SAF. Multivariate regression models were performed adjusted for age, sex, BMI, creatinine, smoking status, and presence of diabetes and additionally for BMD with interaction terms to test for effect modification. Prevalence of MOFs was 8.5% and of VFs 7%. SAF had a curvilinear association with prevalent MOFs and VFs and therefore, age-adjusted, sex stratified SAF quartiles were used. The odds ratio (OR) (95% confidence interval [CI]) of the second, third and fourth quartiles of SAF for MOFs were as follows: OR 1.60 (95% CI, 1.08-2.35; p = .02); OR 1.30 (95% CI, 0.89-1.97; p = .20), and OR 1.40 (95% CI, 0.95-2.10; p = .09), respectively, with first (lowest) quartile as reference. For VFs the ORs were as follows: OR 1.69 (95% CI, 1.08-2.64; p = .02), OR 1.74(95% CI, 1.11-2.71; p = .01), and OR 1.73 (95% CI, 1.12-2.73; p = .02) for second, third, and fourth quartiles, respectively. When comparing the top three quartiles combined with the first quartile, the OR (95% CI) for MOFs was 1.43 (95% CI, 1.04-2.00; p = .03) and for VFs was 1.72 (95% CI, 1.18-2.53; p = .005). Additional adjustment for BMD did not change the associations. In conclusion, there is evidence of presence of a threshold of skin AGEs below which there is distinctly lower prevalence of fractures. Longitudinal analyses are needed to confirm our cross-sectional findings. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Project description:BackgroundAdvanced glycation end products (AGEs) have been linked to cardiovascular disease (CVD), especially coronary heart disease (CHD), but their role in CVD pathogenesis remains unclear. Therefore, we investigated cross-sectional associations of skin AGEs with subclinical atherosclerosis, arterial stiffness, and hypertension after confirming their relation with CHD.MethodsIn the population-based Rotterdam Study, skin AGEs were measured as skin autofluorescence (SAF). Prevalent MI was obtained from digital medical records. Carotid plaques, carotid intima-media thickness (IMT), coronary artery calcification (CAC), pulse wave velocity (PWV), and hypertension were assessed. Associations of SAF with endophenotypes were investigated in logistic and linear regression models adjusting for common cardiovascular risk factors. Effect modification by sex, diabetes mellitus, and chronic kidney disease (CKD) was tested.Results3001 participants were included (mean age 73 (SD 9) years, 57% women). One unit higher SAF was associated with the presence of carotid plaques (OR 1.2 (0.92, 1.57)), a higher max IMT (0.08 SD (0.01, 0.15)), higher CAC (OR 2.2 (1.39, 3.48)), and PWV (0.09 SD (0.01, 0.16)), but not with hypertension (OR 0.99 (0.81, 1.21)). The associations with endophenotypes were more pronounced in men and participants with diabetes or CKD with significant interactions.ConclusionsPreviously documented associations between SAF and CVD, also found in our study, may be explained by the endophenotypes atherosclerosis and arterial stiffness, especially in men and individuals with diabetes or CKD, but not by hypertension. Longitudinal studies are needed to replicate these findings and to test if SAF is an independent risk factor or biomarker of CVD.Trial registrationThe Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl ) and the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/ ) under shared catalogue number NTR6831.

Project description:BACKGROUND:Advanced glycation end products (AGEs) accumulate in tissues with age and in conditions such as diabetes mellitus and chronic kidney disease (CKD), and they may be involved in age-related diseases. Skin AGEs measured as skin autofluorescence (SAF) are a noninvasive reflection of long-term AGE accumulation in tissues. Whether AGEs present in the diet (dAGEs) contribute to tissue AGEs is unclear. OBJECTIVES:Our aim was to investigate the association between dietary and skin AGEs in the Rotterdam Study, a population-based cohort of mainly European ancestry. METHODS:In 2515 participants, intake of 3 dAGEs [carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL)] was estimated using FFQs and the content of AGEs measured in commonly consumed foods. SAF was measured 5 y (median value) later using an AGE Reader. The association of dAGEs with SAF was analyzed in linear regression models and stratified for diabetes and chronic kidney disease (CKD, defined as estimated glomerular filtration rate ≤60 mL/min) status. RESULTS:Mean ± SD intake was 3.40 ±0.89 mg/d for CML, 28.98 ±7.87 mg/d for MGH1, and 3.11 ±0.89 mg/d for CEL. None of them was associated with SAF in the total study population. However, in stratified analyses, CML was positively associated with SAF after excluding both individuals with diabetes and individuals with CKD: 1 SD higher daily CML intake was associated with a 0.03 (95% CI: 0.009, 0.05) arbitrary units higher SAF. MGH1 and CEL intake were not significantly associated with SAF. Nevertheless, the associations were stronger when the time difference between dAGEs and SAF measurements was shorter. CONCLUSIONS:Higher dietary CML intake was associated with higher SAF only among participants with neither diabetes nor CKD, which may be explained by high AGE formation in diabetes and decreased excretion in CKD or by dietary modifications in these disease groups. The dAGE-SAF associations were also modified by the time difference between measurements. Our results suggest that dAGEs can influence tissue AGE accumulation and possibly thereby age-related diseases. This trial was registered at the Netherlands National Trial Register as NTR6831 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831) and at the WHO International Clinical Trials Registry Platform as NTR6831 (http://www.who.int/ictrp/network/primary/en/).

Project description:Advanced glycation end products (AGEs) accumulate in tissues with aging and may influence age-related diseases. They can be estimated non-invasively by skin autofluorescence (SAF) using the AGE Reader™. Serum 25-hydroxyvitamin D3 (25(OH)D3) may inhibit AGEs accumulation through anti-oxidative and anti-inflammatory properties but evidence in humans is scarce. The objective was to investigate the association between serum 25(OH)D3 and SAF in the population-based cohort study. Serum 25(OH)D3 and other covariates were measured at baseline. SAF was measured on average 11.5 years later. Known risk factors for AGE accumulation such as higher age, BMI, and coffee intake, male sex, smoking, diabetes, and decreased renal function were measured at baseline. Linear regression models were adopted to explore the association between 25(OH)D3 and SAF with adjustment for confounders. Interaction terms were tested to identify effect modification. The study was conducted in the general community. 2746 community-dwelling participants (age ≥ 45 years) from the Rotterdam Study were included. Serum 25(OH)D3 inversely associated with SAF and explained 1.5% of the variance (unstandardized B = - 0.002 (95% CI[- 0.003, - 0.002]), standardized β = - 0.125), independently of known risk factors and medication intake. The association was present in both diabetics (B = - 0.004 (95% CI[- 0.008, - 0.001]), β = - 0.192) and non-diabetics (B = - 0.002 (95% CI[- 0.003, - 0.002]), β = - 0.122), both sexes, both smokers and non-smokers and in each RS subcohort. Serum 25(OH)D3 concentration was significantly and inversely associated with SAF measured prospectively, also after adjustment for known risk factors for high SAF and the number of medication used, but the causal chain is yet to be explored in future studies.Clinical Trial Registry (1) Netherlands National Trial Register: Trial ID: NTR6831 ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 ). (2) WHO International Clinical Trials Registry Platform: under shared catalogue number NTR6831 ( www.who.int/ictrp/network/primary/en/ ).

Project description:The metabolic syndrome (MetS) comprises several cardiometabolic risk factors associated with increased risk for both type 2 diabetes and cardiovascular disease. Skin autofluorescence (SAF), a non-invasive biomarker of advanced glycation end products accumulation, is associated with cardiovascular complications in subjects with diabetes. The aim of the present study was to examine the association between SAF and the presence of MetS as well as its individual components in a general population.For this cross-sectional analysis, we included 78,671 non-diabetic subjects between 18 and 80 years of age who participated in the LifeLines Cohort Study and had SAF measurement obtained non-invasively using the AGE Reader. MetS was defined according to the revised NCEP ATP III criteria. Students unpaired t test was used to test differences between groups. Both logistic and linear regression analyses were performed in order to test associations between the individual MetS components and SAF.Subjects with MetS had higher SAF (2.07 ± 0.45 arbitrary units, AU) compared to individuals without MetS (1.89 ± 0.42 AU) (p < 0.001). There was a positive association between the number of MetS components and higher SAF Z-scores (p < 0.001). Individuals in the highest SAF tertile had a higher presence of MetS (OR 2.61; 95% CI 2.48-2.75) and some of the individual components compared to subjects in the lowest SAF tertile. After correction for age, gender, creatinine clearance, HbA1c and smoking status, only elevated blood pressure and low HDL cholesterol remained significantly associated with higher SAF (p = 0.002 and p = 0.001 respectively).Skin autofluorescence was associated with the presence of MetS and some of its individual components. In addition, increasing SAF Z-scores were observed with a higher number of MetS components. Prospective studies are needed to establish whether SAF can be used as an (additional) screening tool to predict both cardiovascular disease and type 2 diabetes in high-risk populations.

Project description:BackgroundAdvanced glycation end products (AGEs) are involved in age-related diseases, but the interaction of gut microbiota with dietary AGEs (dAGEs) and tissue AGEs in the population is unknown.ObjectiveOur objective was to investigate the association of dietary and tissue AGEs with gut microbiota in the population-based Rotterdam Study, using skin AGEs as a marker for tissue accumulation and stool microbiota as a surrogate for gut microbiota.DesignDietary intake of three AGEs (dAGEs), namely carboxymethyl-lysine (CML), N-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MGH1), and carboxyethyl-lysine (CEL), was quantified at baseline from food frequency questionnaires. Following up after a median of 5.7 years, skin AGEs were measured using skin autofluorescence (SAF), and stool microbiota samples were sequenced (16S rRNA) to measure microbial composition (including alpha-diversity, beta-dissimilarity, and taxonomic abundances) as well as predict microbial metabolic pathways. Associations of both dAGEs and SAF with microbial measures were investigated using multiple linear regression models in 1052 and 718 participants, respectively.ResultsdAGEs and SAF were not associated with either the alpha-diversity or beta-dissimilarity of the stool microbiota. After multiple-testing correction, dAGEs were not associated with any of the 188 genera tested, but were nominally inversely associated with the abundance of Barnesiella, Colidextribacter, Oscillospiraceae UCG-005, and Terrisporobacter, in addition to being positively associated with Coprococcus, Dorea, and Blautia. A higher abundance of Lactobacillus was associated with a higher SAF, along with several nominally significantly associated genera. dAGEs and SAF were nominally associated with several microbial pathways, but none were statistically significant after multiple-testing correction.ConclusionsOur findings did not solidify a link between habitual dAGEs, skin AGEs, and overall stool microbiota composition. Nominally significant associations with several genera and functional pathways suggested a potential interaction between gut microbiota and AGE metabolism, but validation is required. Future studies are warranted, to investigate whether gut microbiota modifies the potential impact of dAGEs on health.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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