Glyoxal-derived advanced glycation end products (GO-AGEs) with UVB critically induce skin inflammaging: in vitro and in silico approaches

Abstract

Advanced glycation end products (AGEs) have potential implications on several diseases including skin inflammation and aging. AGEs formation can be triggered by several factors such as UVB, glyoxal and methylglyoxal etc. However, little attention has been paid to glyoxal-derived AGEs (GO-AGEs) and UVB-induced skin inflammaging, with none have investigated together. This study aimed to investigate the possible role of GO-AGEs and UVB in skin inflammaging focusing on revealing its molecular mechanisms. The effects of GO-AGEs in the presence or absence of UVB were studied by using enzyme linked immunosorbent assay, western blotting, qPCR, flow cytometry and in silico approaches. In HaCaT cells, GO-AGEs in the presence of UVB irradiation (125 mJ/cm2) dramatically enhanced the release of different pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) with further activation of RAGE signaling pathways (NF-κB, COX 2, and IL- 1β) and increased oxidative stress also noticed in NHEK cells. In NHDF cells, extracellular matrix disruption noted via increasing matrix metalloproteinase release and decreasing collagen type 1 and SIRT1 expression. Besides that, the docking scores obtained from the molecular docking study support the above-mentioned results. This study strongly suggests the pivotal role of GO-AGEs in skin inflammaging and illuminates novel molecular pathways for searching most effective and updated anti-aging therapy.

Associations between Skin Autofluorescence Levels with Cardiovascular Risk and Diabetes Complications in Patients with Type 2 Diabetes

“…Advanced Glycation End Products (AGEs) are detrimental byproducts of hyperglycemia in diabetes mellitus (DM) and aging in the non-diabetic population, with their accumulation exacerbating glucose metabolism imbalances, metabolic syndrome (MetS), and chronic diseases, including cardiovascular (CV) disease, chronic kidney disease (CKD), and neurodegenerative disorders [1][2][3][4][5][6][7][8][9]. These products are formed through the nonenzymatic glycation of biomolecules, such as proteins, lipids, and nucleic acids, with an alternative pathway involving the reaction with α-dicarbonyl compounds, which are highly reactive and able to establish covalent bonds [3,10,11].…”