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Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans.

ABSTRACT: To assess the utility of autofluorescence as a noninvasive biomarker of senescence in Caenorhabditis elegans, we measured the autofluorescence of individual nematodes using spectrofluorometry. The fluorescence of each worm increased with age. Animals with lower fluorescence intensity exhibited longer life expectancy. When proteins extracted from worms were incubated with sugars, the fluorescence intensity and the concentration of advanced glycation end products (AGEs) increased over time. Ribose enhanced these changes not only in vitro but also in vivo. The glycation blocker rifampicin suppressed this rise in fluorescence. High-resolution mass spectrometry revealed that vitellogenins accumulated in old worms, and glycated vitellogenins emitted six-fold higher fluorescence than naive vitellogenins. The increase in fluorescence with ageing originates from glycated substances, and therefore could serve as a useful noninvasive biomarker of AGEs. C. elegans can serve as a new model to look for anti-AGE factors and to study the relationship between AGEs and senescence.

SUBMITTER: Komura T

PROVIDER: S-EPMC8184826 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans.

Komura Tomomi T Yamanaka Mikihiro M Nishimura Kohji K Hara Keita K Nishikawa Yoshikazu Y

NPJ aging and mechanisms of disease 20210607 1

To assess the utility of autofluorescence as a noninvasive biomarker of senescence in Caenorhabditis elegans, we measured the autofluorescence of individual nematodes using spectrofluorometry. The fluorescence of each worm increased with age. Animals with lower fluorescence intensity exhibited longer life expectancy. When proteins extracted from worms were incubated with sugars, the fluorescence intensity and the concentration of advanced glycation end products (AGEs) increased over time. Ribose ...[more]

PMID: 34099724

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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: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.

Dataset Information

Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans.

Publications

Autofluorescence as a noninvasive biomarker of senescence and advanced glycation end products in Caenorhabditis elegans.

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