Changes in gene expression patterns in young and senescent fibroblasts in glycated three-dimensional collagen matrices
Glycation, or non-enzymatic glycosylation, has recently attracted increasing interest in the context of its impact on aging. Advanced glycation end products (AGEs) contribute to various age-related pathological conditions such as inflammation, fibrosis, stem cell aging, etc. However, the molecular mechanisms underlying the glycation-induced disruption of cell-matrix interactions during cellular senescence are not fully understood. The aim of this study was to investigate transcriptomic changes in young and senescent dermal fibroblasts (HdFbs) cultivated in post-glycated 3D collagen type I matrices after 10 and 17 days. Our findings indicate that the D-ribose-mediated glycation increases the accumulation of fluorescent AGEs and the stiffness of the matrices in a dose-dependent manner. The transcriptome alterations encompassed the modulation of age-related genes and signaling pathways, including the activation of genes related to senescence-associated secretory phenotype (SASP) in young cells. Notably, the alterations in the transcriptome profiles due to glycation were more pronounced (in terms of both the number of genes and their fold changes) on day 10 of cultivation compared to day 17 in both passages. Overall design: We performed RNA-Seq to analyze the effect of D-ribose, as glycating agent, on gene expression profiles of normal fibroblasts on different stages of cell senescence. To assess the transcriptomic changes, we used human dermal fibroblasts (HdFb (d75)) at 12th (consider as “young”) and 20th (consider as “senescent”) passages cultured for 10 and 17 days inside 3D post-glycated collagen matrices.