Age-Dependent Morphofunctional Regenerative Activity of Skin Dermal Fibroblasts

Chronological aging is defined as the time-dependent decline in tissue homeostasis, which significantly affects the skin. Elucidating the mechanisms of skin aging is a priority in modern research, though limited by the lack of appropriate in vitro models. As a component of aging, replicative or stress-induced senescence is widely used to simulate skin aging in vitro. The aim of the study is a comparative assessment of age-related morphological and molecular changes in primary cultured fibroblasts derived from individuals over 45 years old and under 15 years old. Material and methods. This study investigated primary normal human dermal fibroblasts isolated from young and elderly donors, focusing on their age-related characteristics during 2D monolayer culture and their potential use as a relevant model for studying aging processes. We employed fluorimetry to analyze proliferation, assessed clonogenic activity, and evaluated various indicators of regenerative potential, including elastase activity, gene expression, and mitochondrial DNA (mtDNA) content. Data were statistically analyzed using multiple descriptive statistics. Differences were considered statistically significant at p<0.05. Results. A marked decline in the population doubling ability, reduced clonogenic capacity, impaired extracellular matrix production along with modifications in respiratory metabolism were observed with increasing age. These impairments were particularly evident when comparing fibroblasts isolated from individuals over 45 years old with those from participants younger than 15 years, while cells from middle-aged donors exhibited an intermediate profile. Conclusions. The observed changes in cell properties may be associated with signs of dermal aging, supporting the assumption that cultured primary cells indeed retain some characteristics of the original tissue from which they were derived. The findings have both scientific and practical significance for modeling studies on the mechanisms of aging, understanding the mechanisms of regenerative repair at different ages, and for targeted interventions, such as in the treatment of gingival recession in patients of varying ages.

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