Work

Dissecting the reciprocal association between cytoskeletal mechanics and senescence-associated phenotypes in human dermal fibroblasts

Year: 2026

Type: article

Abstract: Introduction: Cellular mechanical properties play crucial roles in governing cellular functions, with their dynamic changes influenced by various factors including physiological and pathological states. Skin photoaging is closely linked to fibroblast senescence and extracellular matrix (ECM) dysfunction, yet the interplay between cellular senescence and cytoskeletal mechanics remains poorly understood. This study aimed to characterize cytoskeletal mechanical changes and explore whether maintaining F-actin cytoskeletal stability could attenuate senescent phenotypes in photoaged human dermal fibroblasts (HDFs). Methods: A model of HDFs with senescence-associated phenotypes was established by ultraviolet B (UVB) irradiation. Micromechanical properties of UVB-irradiated HDFs were evaluated using integrated cellular, molecular, and biophysical approaches, encompassing the analysis of cellular apparent modulus, cell-mediated ECM contraction, and actin cytoskeletal contractile units. Latrunculin A (LAT-A) and Jasplakinolide (JASP) were employed for targeted remodeling of the F-actin cytoskeleton to evaluate their effects on cellular senescence-associated markers. Results: UVB-irradiated HDFs with senescence-associated phenotypes exhibited reduced apparent Young's modulus, impaired F-actin polymerization and organization, diminished myosin II regulatory light chain phosphorylation, and compromised collagen matrix contraction. Disruption of F-actin polymerization with LAT-A in young HDFs was accompanied by the appearance of cellular senescence markers, including upregulation of p21 and MMP1, downregulation of Lamin B1 and COL I. Conversely, stabilizing F-actin with JASP in UVB-exposed HDFs attenuated these changes, preserved spindle-shaped cellular morphology, and reduced the expression of senescence markers. Discussion: Our findings confirm that UVB-induced senescence-associated phenotypes in HDFs are accompanied by impaired F-actin cytoskeletal mechanics, and pharmacological modulation of F-actin partially alters multiple senescence-associated markers. These findings provide theoretical evidence and potential intervention strategies to disrupt the establishment of the UVB-induced senescent phenotype in HDFs.

Source: Frontiers in Physiology

DOI: 10.3389/fphys.2026.1882078