Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans.
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ABSTRACT:
SUBMITTER: Komura T
PROVIDER: S-EPMC8184826 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAccumulation of advanced glycation end-products (AGEs) in skeletal muscle has been implicated in development of sarcopenia.AimTo obtain further insight in the pathophysiology of sarcopenia, we studied its relationship with skin AGEs in the general population.MethodsIn 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 as skin autofluorescence (SAF) using AGE ReaderTM, appendicular skeletal mass index (ASMI) using insight dual-energy X-ray absorptiometry, hand grip strength (HGS) using a hydraulic hand dynamometer, and, in a subgroup, gait speed (GS) measured on an electronic walkway (n = 2080). We defined probable sarcopenia (low HGS) and confirmed sarcopenia (low HGS and low ASMI) based on the European Working Group on Sarcopenia in Older People (EWGSOP2) revised criteria cutoffs. Multivariate linear and logistic regression were performed adjusting for age, sex, body fat percentage, height, renal function, diabetes, and smoking status.ResultsThe prevalence of low ASMI was 7.7%; probable sarcopenia, 24%, slow GS, 3%; and 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)]. A 1-unit increase in SAF was associated with higher odds of probable sarcopenia [odds ratio (OR) 1.36 (95% CI 1.09, 1.68)] and confirmed sarcopenia [OR 2.01 (95% CI 1.33, 3.06)].ConclusionHigher 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.
| S-EPMC8764216 | biostudies-literature
Project description:BackgroundAccumulation 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.MethodsA 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.ResultsThe 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]).ConclusionsHigher 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.
| S-EPMC9536452 | biostudies-literature
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.
| S-EPMC7687120 | biostudies-literature
Project description:Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.
| S-EPMC4406675 | biostudies-literature
Project description:Advanced glycation end products (AGEs) are thought to play important roles in the pathogenesis of diabetic microangiopathy, particularly in the progression of diabetic retinopathy (DR). We assessed the levels of skin autofluorescence (sAF) to assess the association between AGEs and DR stages. A total of 394 eyes of 394 Japanese subjects (172 men, 222 women; mean age ± standard deviation [SD], 68.4 ± 13.7 years) comprised the study population, i.e., subjects with diabetes mellitus (DM) (n = 229) and non-diabetic controls (n = 165). The patients with DM were divided into those without DR (NDR, n = 101) and DR (n = 128). DR included simple (SDR, n = 36), pre-proliferative (PPDR, n = 25), and PDR (n = 67). Compared to controls (0.52 ± 0.12), the AGE scores were significantly higher in patients with DM (0.59 ± 0.17, p < 0.0001), NDR (0.58 ± 0.16, p = 0.0012), and DR (0.60 ± 0.18, p < 0.0001). The proportion of patients with PDR was significantly higher in the highest quartile of AGE scores than the other quartiles (p < 0.0001). Compared to those without PDR (SDR and PPDR), those with PDR were younger (p = 0.0006), more were pseudophakic (p < 0.0001), had worse visual acuity (VA) (p < 0.0001), had higher intraocular pressure (IOP) (p < 0.0001), and had higher AGE scores (p = 0.0016). Multivariate models also suggested that younger age, male gender, pseudophakia, worse VA, higher IOP, and higher AGE scores were risk factors for PDR. The results suggested that AGE scores were higher in patients with DM and were independently associated with progression of DR. In addition, more PDR was seen in the highest quartile of AGE scores. This study highlights the clinical use of the AGE score as a non-invasive, reliable marker to identity patients at risk of sight-threatening DR.
| S-EPMC7695256 | biostudies-literature
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.
| S-EPMC10685533 | biostudies-literature
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.
| S-EPMC5450154 | biostudies-other
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM). mRNA profiles of Primary human posterior longitudinal ligament cells stimulated with various stimuli (Control, 1µM AGE-BSA, 5µM AGE-BSA, 1µM AGE-BSA with BMP2, 5µM AGE-BSA with BMP2) were generated by deep sequencing on Ion Proton
2016-02-16 | E-GEOD-65952 | biostudies-arrayexpress
Project description:Ossification of the posterior longitudinal ligament (OPLL) is formed by heterogeneous ossification of posterior longitudinal ligament. The patho-mechanism of OPLL is still largely unknown. Recently, disorders of metabolism are thought to be the center of many diseases such as OPLL. Advanced glycation end product (AGE) are accumulated in many extracellular matrixes such as ligament fibers, and it can functions as cellular signal through its receptor (RAGE), contributing to various events such as atherosclerosis or oxidative stress. However, its role in OPLL formation is not yet known. Therefore, we performed high-through-put RNA sequencing on primary posterior longitudinal ligament cells treated with different doses of AGEs (1µM, 5µM and negative control), with or without BMP2 (1µM).
2016-02-16 | GSE65952 | GEO
Project description:This study was aimed to correlate the pre- and 6-month postpercutaneous coronary intervention (PCI) serum concentrations of advanced glycation end products (AGE), soluble receptors for advanced glycation end products (sRAGE), AGE/sRAGE ratio, and serum malondialdehyde (MDA) levels with in-stent restenosis (ISR) among patients receiving either a drug-eluting stent (DES) or a bare-metal stent (BMS).In-stent restenosis remains as an adverse outcome following PCI. Sixty consecutive nondiabetic, Caucasian male patients, diagnosed with a non-ST-elevation myocardial infarction who received either a DES or BMS via PCI, were enrolled. Baseline levels of serum AGE, sRAGE, AGE/sRAGE ratios, MDA, and angiographic parameters were determined at stenting and at 6 months. Patients with and without ISR at 6 months were compared on both baseline and 6-month biomarker levels and within stent types.The pre-PCI serum AGE levels and AGE/sRAGE ratios were higher in ISR patients compared with non-ISR patients, while the pre-PCI and post-PCI serum sRAGE levels were lower in ISR patients compared with non-ISR patients. The pre and post-PCI levels of MDA were also higher in ISR patients. Comparing stent types, relative levels of MDA between those with and without ISR at the respective time points were similar, although changes between time points appeared type specific.Post-PCI ISR correlates with low serum values of sRAGE and high serum values of AGE, MDA, and AGE/sRAGE ratio which are present at stenting. The associations of baseline AGE, sRAGE, AGE/sRAGE, and MDA levels with ISR appear consistent between stent types.
| S-EPMC6221796 | biostudies-literature