The results describe a cell-culture model, not a treatment for human skin aging, and do not establish a complete causal pathway between ultraviolet stress, actin remodeling and senescence. The study examined human dermal fibroblasts, the cells responsible for producing extracellular-matrix components and applying tension to the surrounding dermis. Investigators established a senescence-like model by exposing these cells to 150 millijoules per square centimeter of UVB radiation, either once or twice at 24-hour intervals, with the second exposure following the first by a day.

The principal experiments were performed 24 hours after the final exposure. The irradiated cells developed several characteristics used by the researchers to classify senescence-associated phenotypes: increased senescence-associated beta-galactosidase staining, higher p21 expression, reduced Lamin B1 and collagen I, increased matrix metalloproteinase 1, fewer Ki67-positive cells and elevated gamma-H2AX, a marker of DNA damage. A single exposure reduced cellular metabolic activity by approximately 30%, compared with about 50% after repeated exposure.

Single-cell nanoindentation showed that the mechanical changes accompanied these molecular and functional markers. Young fibroblasts had an apparent Young’s modulus of approximately 4.3 kilopascals, compared with about 2.9 kilopascals after one UVB exposure and 2.5 kilopascals after two exposures. Measurements in peripheral cytoplasm showed a similar pattern, with higher absolute values than those recorded in the perinuclear region.

The reported modulus should be interpreted as an apparent, loading-rate-dependent stiffness rather than an intrinsic elastic constant. The Hertz model used to fit the force-indentation curves assumes a linearly elastic, homogeneous, isotropic and passive material, whereas living fibroblasts are viscoelastic, structurally heterogeneous and pre-stressed. The researchers tested 20–40 randomly selected individual cells per group using a spherical probe with a radius of 3 micrometers and a maximum load of 0.03 micronewtons.

Fibroblasts also became less able to deform their surroundings. In rat-tail type I collagen gels, young cells produced approximately 80% contraction at 24 hours, compared with about 70% in the group exposed to UVB once and 43% in the group exposed twice. The decrease was evident at each of the assay’s five observation points, from 0.5 to 48 hours.

Lower alpha-smooth muscle actin expression, a marker associated with the fibroblast contractile phenotype, and reduced phosphorylation of myosin regulatory light chain were consistent with this functional weakening. Myosin II generates cytoskeletal tension through its interaction with F-actin, and the drop in phosphorylated myosin light chain provided a molecular correlate of the reduced contraction. Replication-induced senescent fibroblasts showed similar trends in apparent modulus, collagen contraction, actin assembly and myosin activity, although the principal analyses focused on the UVB model.

Fluorescence imaging identified changes in the structure and organization of the actin cytoskeleton. Young fibroblasts displayed dense, well-aligned stress fibers, while irradiated cells had sparse, disordered filaments and a marked loss of the perinuclear actin cap. Their shape shifted from an elongated spindle toward a spread, irregular polygonal form, accompanied by greater lateral spreading.

The F-actin-to-G-actin ratio declined even though total actin levels did not change, indicating impaired polymerization or organization rather than a simple reduction in actin abundance. Irradiated cells also had higher cofilin-1, lower coronin-1C and filamin B, and reduced cofilin phosphorylation. Together, these observations pointed to altered regulation of filament assembly, cross-linking and turnover rather than loss of the total actin pool.

The timing of the damage and mechanical responses suggested that they were not interchangeable measures of the same process. Gamma-H2AX increased markedly two hours after irradiation but had declined by 24 hours, while F-actin depolymerization and the reduction in apparent Young’s modulus became statistically significant at 24 hours. DNA-damage signaling remained detectable for as long as seven days after irradiation, but apparent stiffness did not change significantly over that interval.

The authors proposed that DNA damage might act as an initiating trigger for mechanical remodeling rather than as a sustained quantitative driver of stiffness. They explicitly described that interpretation as a hypothesis requiring further validation, and the experiments did not directly test the sequence or any molecular link between persistent DNA damage and actin remodeling. To examine the reciprocal side of the association, the researchers treated young fibroblasts with latrunculin A, an inhibitor of F-actin polymerization.

The treatment reduced filamentous actin, weakened the perinuclear actin network, lowered apparent Young’s modulus and diminished myosin light-chain phosphorylation. It was also accompanied by increased p21 and matrix metalloproteinase 1, decreased Lamin B1 and collagen I, lower alpha-smooth muscle actin and a reduced Ki67-positive fraction. These observations showed that disruption of actin assembly was associated with several features seen in the UVB model.

After the drug was removed and the cells recovered in drug-free medium for 24 hours, the actin cytoskeleton recovered and p21, Lamin B1, matrix metalloproteinase 1 and phosphorylated myosin light chain returned toward control levels. A separate myosin II inhibitor, blebbistatin, also changed p21 and Lamin B1 levels and the Ki67-positive rate. In the complementary experiment, fibroblasts were pretreated with jasplakinolide, an F-actin-stabilizing compound, before UVB exposure.

Jasplakinolide partially preserved the elongated, spindle-like shape of irradiated cells, limited excessive spreading, protected apparent Young’s modulus and maintained F-actin polymerization and myosin activity. Relative to untreated UVB-exposed fibroblasts, it also reduced the UVB-associated loss of Ki67, lowered p21 and matrix metalloproteinase 1 expression and increased collagen I expression. These findings do not demonstrate that jasplakinolide reverses senescence or prevents skin aging.

Instead, they show that pharmacological modulation of actin assembly partially changed mechanical properties and selected senescence-associated markers in cultured fibroblasts exposed to UVB. Several limitations constrain the interpretation of the intervention experiments. Latrunculin A and jasplakinolide affect cellular processes beyond the direct mechanical contribution of F-actin, including adhesion, contractility and cell-cycle progression, making it difficult to isolate the role of mechanical tension itself.

The study also did not establish whether applied mechanical cues alone are sufficient to regulate the measured markers; the authors proposed future experiments using mechanical stretching or substrates with tunable stiffness to address that question. Senescent-cell mechanics vary with cell type, the method of inducing senescence, the cellular environment, measurement time and testing platform. The source noted that increased stiffness has been reported in some epithelial cells and aged fibroblasts, while increased traction force—not increased stiffness—has been documented in endothelial cells.

Replicatively senescent fibroblasts in this study resembled the UVB model, but the broader literature does not support one universal mechanical signature for senescence. Within those boundaries, the experiments provide a coherent picture of how the UVB-associated phenotype and cytoskeletal mechanics relate. UVB exposure was accompanied by senescence-related molecular changes, reduced apparent stiffness, weaker collagen contraction, disorganized F-actin and diminished myosin activity.

Breaking F-actin assembly in young cells reproduced several of those features, while protecting F-actin during UVB exposure partially mitigated them. The evidence therefore supports a reciprocal association between cytoskeletal mechanics and senescence-associated phenotypes, rather than a proven linear mechanism. The authors hypothesize that integrin signaling, the RhoA–ROCK axis, stress-fiber assembly and mechanotransduction pathways such as YAP/TAZ may help connect ultraviolet stress to altered nuclear signaling and extracellular-matrix function, but those links were not established directly.

Subject of Research: Experimental study of F-actin organization, cellular mechanics and senescence-associated markers in UVB-exposed human dermal fibroblasts

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

Article References: Tang, H., Qian, R., Wang, N., Pan, Y., Xuan, L., Wang, J., Huang, H., & Zhang, X. (2026). Dissecting the reciprocal association between cytoskeletal mechanics and senescence-associated phenotypes in human dermal fibroblasts. Frontiers in Physiology, 17, Article 1882078. https://doi.org/10.3389/fphys.2026.1882078

Image Credits: AI Generated

DOI: 10.3389/fphys.2026.1882078

Keywords: UVB exposure, human dermal fibroblasts, F-actin organization, cellular senescence, cellular mechanics, extracellular matrix, collagen contraction, photoaging, myosin II, jasplakinolide, Dissecting, reciprocal