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, and vascular calcification. However, the molecular mechanisms underlying 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) cultured in 3D post-glycated collagen type I matrices after 10 and 17 days. Our findings indicate that D-ribose-mediated glycation increases the accumulation of fluorescent AGEs and the stiffness of matrices in a dose-dependent manner. The transcriptome alterations in cells encompassed the modulation of age-related genes and signaling pathways, including activation of genes related to senescence-associated secretory phenotype (SASP). 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) after 10 days of culture compared to day 17 in both passages. These findings suggest that cellular responses to glycation and resulting stiffness depend on both the concentration of reducing sugar and the time spent under those conditions.