Abstract
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/).
Highlights
Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidized end products formed through non-enzymatic attachment of sugars to free amino groups of proteins, lipids and nucleic acids [1, 2]
Multiple linear regression analyses were conducted with skin autofluorescence (SAF) being the outcome, whilst adjusting for covariates that may confound the association or potential risk factors for high SAF
Because vitamin D may prevent AGEs accumulation through its anti-inflammatory properties, we studied in a large prospective cohort whether serum 25(OH)D3 concentration at baseline was associated with AGEs in the skin assessed by SAF at follow-up
Summary
Advanced glycation end products (AGEs) are a heterogeneous group of highly oxidized end products formed through non-enzymatic attachment of sugars to free amino groups of proteins, lipids and nucleic acids [1, 2]. AGEs accumulation contributes to the aging process [8] and age-related diseases [4] through formation of covalent crosslinking of proteins in the extracellular matrix such as collagen and elastin which lead to tissue stiffening, influencing molecules’ functions by binding to active sites of molecules, and inducing inflammation and cellular dysfunction through interaction with the receptor for AGEs [4, 9]. They may have genotoxic effects [10]. Aside from the involvement in diabetic complications such as renal insufficiency and neuropathy [11], AGEs have been implicated in cardiovascular disease [12], bone pathology [13], lung diseases [14], neurodegenerative diseases [15] and some types of cancer [16]
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