Background Accumulation of advanced glycation end-products (AGEs) in skeletal muscle has been implicated in development of sarcopenia. Aim To obtain further insight in the pathophysiology of sarcopenia we studied its relationship with skin AGEs in the general population. Methods In a cross-sectional analysis, 2744 participants of Northern European background, mean age 74.1 years were included from the Rotterdam Study. Skin AGEs were measured using AGE readerTMas Skin autofluorescence (SAF), appendicular skeletal mass index (ASMI) using iDXA, hand grip strength (HGS) using a hydraulic hand dynamometer and in a subgroup gait speed (GS) measured on an electronic walkway (n=2,080). We defined probable sarcopenia (low HGS) and confirmed sarcopenia (low HGS and low ASMI) based on European working group on Sarcopenia revised criteria (EWGSOP2) cut-offs. Multivariate linear and logistic regression were performed adjusting for age, sex, body fat percentage, height, renal function, diabetes and smoking status. Results The prevalence of low ASMI was 7.7%, probable sarcopenia 24%, slow GS 3%, confirmed sarcopenia 3.5%. SAF was inversely associated with ASMI (β=-0.062, 95%CI = -0.092 - -0.032), HGS (β=-0.051, 95%CI = -0.075 - -0.026) and GS (β=-0.074, 95% CI = -0.116 - -0.033). One unit increase in SAF was associated with higher odds of probable sarcopenia (OR = 1.36, 95% CI = 1.09 -1.68) and confirmed sarcopenia (OR = 2.01, 95% CI = 1.33- 3.06). Conclusion Higher skin AGEs are associated with higher sarcopenia prevalence. We call for future longitudinal studies to explore the role of SAF as a potential biomarker of sarcopenia.

This study investigated the removal of ammonia in wastewater by an electrochemical method using titanium electrodes coated with ruthenium and iridium (RuO 2 -IrO 2 -TiO 2 /Ti) with low chlorine evolution overvoltage. The effects of operating parameters, including chloride ion concentration, current density and initial pH, were also investigated. The results were evaluated primarily by considering the efficiency of the elimination of NH 4 + -N. The removal of ammonia by electrochemical oxidation mainly resulted from the indirect oxidation effect of chlorine/hypochlorite produced during electrolysis. The direct anodic oxidation efficiency of ammonia was less than 5%, and the current efficiency was less than 10%. The ammonia removal followed pseudo-first-order kinetics. The electrochemical process can be applied successfully as a final polishing step, or as an alternative method to biological nitrification. The process seems to be most beneficial for small coastal cities

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IMPORTANCE Advanced glycation end products (AGEs) and their receptor (RAGE) are implicated in the pathophysiological processes of dementia and potentially underlie the association of diabetes with neurodegeneration. However, longitudinal studies examining this association are lacking. OBJECTIVE To determine whether markers of the AGE-RAGE system are associated with prevalent and incident dementia and with cognition. DESIGN, SETTING, AND PARTICIPANTS In this population-based cohort study including participants from the prospective Rotterdam Study, extracellular newly identified RAGE binding protein (EN-RAGE) and soluble RAGE (S-RAGE) were measured in plasma collected between 1997 and 1999 in a random selection of participants, and additionally in participants with prevalent dementia. Participants without dementia were followed up for dementia until 2016. Skin AGEs,

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.

ABSTRACT 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/).

Animal studies suggest a role for dietary advanced glycation end-products (dAGEs) in bone health, but human studies on dAGEs in relation to bone are lacking. We aimed to study whether dAGEs intake is associated with the parameters of bone strength namely, bone mineral density (BMD), prevalent vertebral (VFs), and major osteoporotic fractures (MOFs = hip, wrist, proximal humerus, and clinical VFs). 3949 participants (mean age 66.7 ± 10.5 years) were included from a Rotterdam study for whom Carboxymethyllysine (CML—a dietary AGE) was estimated from food frequency questionnaires combined with dAGEs databases. Multivariable linear and logistic regression models were performed adjusting for age, sex, energy intake, dietary quality, physical activity, diabetes, smoking, renal function, and cohort effect and for models on fractures, subsequently for BMD. We observed no association of CML with BMD at both femoral neck (β = −0.006; p = 0.70) and lumbar spine (β = −0.013; p = 0.38). A higher intake of CML was linearly associated with VFs (Odds ratio, OR = 1.16, 95% CI (1.02–1.32) and a similar but non-significant trend with MOFs (OR = 1.12 (0.98–1.27). Additional adjustment for BMD did not change the associations. Our results imply a positive association between dietary intake of CML and VFs independent of BMD. Future studies are needed in order to elucidate whether associations found are causal.

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 AGEs accumulation and frailty. Methods A cross-sectional analysis was performed on 2521 participants from Rotterdam study. Skin AGEs were assessed as skin autofluorescence (SAF) using the AGE readerTM. We used two 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 pre-frailty (presence of ≤2 components). Rockwood’s concept including 38 deficits from physical and psychosocial health domains, was used to calculate 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 and smoking status. Results Mean SAF was 2.39 ± 0.49 AU and median age 74.2 (14.0) years. Regarding physical frailty, 96 persons (4%) were frail and 1221 (48%) pre-frail. SAF was associated with both being pre-frail [odds ratio (95% confidence interval) = 1.29 (1.07 – 1.56)] and frail [1.87 (1.20 – 2.90)] compared with non-frail. Regarding 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)]. Conclusion 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.