Stiffening of Human Skin Fibroblasts with Age

Abstract

Changes in mechanical properties are an essential characteristic of the aging process of human skin. Previous studies attribute these changes predominantly to the altered collagen and elastin organization and density of the extracellular matrix. Here, we show that individual dermal fibroblasts also exhibit a significant increase in stiffness during aging in vivo. With the laser-based optical cell stretcher we examined the viscoelastic biomechanics of dermal fibroblasts isolated from 14 human donors aged 27 to 80. Increasing age was clearly accompanied by a stiffening of the investigated cells. We found that fibroblasts from old donors exhibited an increase in rigidity of ∼60% with respect to cells of the youngest donors. A FACS analysis of the content of the cytoskeletal polymers shows a shift from monomeric G-actin to polymerized, filamentous F-actin, but no significant changes in the vimentin and microtubule content. The rheological analysis of fibroblast-populated collagen gels demonstrates that cell stiffening directly results in altered viscoelastic properties of the collagen matrix. These results identify a new mechanism that may contribute to the age-related impairment of elastic properties in human skin. The altered mechanical behavior might influence cell functions involving the cytoskeleton, such as contractility, motility, and proliferation, which are essential for reorganization of the extracellular matrix.

Cryptomphalus aspersa mollusc eggs extract promotes migration and prevents cutaneous ageing in keratinocytes and dermal fibroblasts in vitro

“…Relating to senescent cells, it has been described that SHDF in vitro are much larger with round and flat appearance compared to that of HDF, produce higher amounts of vimentin and also exhibit decreased adhesion to substrate, because of a lower expression of vinculin and the presence of small focal contact sites [13,14]. All these characteristics have been seen in our SHDF used in this work in contrast to primary HDF cells, which show higher expression of vinculin, more prominent focal adhesion contacts and high production of extracellular matrix proteins, including Col1 and fibronectin ( Figs 5-7), and therefore with increased ability for movement compared with SHDF [14,27]. In addition, Schulze et al [27] found an increase in stiffening with age in HDF cells obtained from human donors that could be related with changes in the organization and density of the extracellular matrix, particularly with alterations in the polymerization state and organization of actin in the cell (balance between G and F-actin).…”

“…All these characteristics have been seen in our SHDF used in this work in contrast to primary HDF cells, which show higher expression of vinculin, more prominent focal adhesion contacts and high production of extracellular matrix proteins, including Col1 and fibronectin ( Figs 5-7), and therefore with increased ability for movement compared with SHDF [14,27]. In addition, Schulze et al [27] found an increase in stiffening with age in HDF cells obtained from human donors that could be related with changes in the organization and density of the extracellular matrix, particularly with alterations in the polymerization state and organization of actin in the cell (balance between G and F-actin). Thereby, whereas young primary cells showed relatively higher amounts of unpolymerized G-actin, the SHDF cells exhibited apparently shorter and thicker actin stress fibres because of their relatively lower levels of G-actin and higher levels of F-actin.…”

Impact of Stratum Corneum Damage on Natural Moisturizing Factor (NMF) in the Skin

“…Maintaining adequate skin fl exibility and elasticity is a primary defense against mechanical damage. Aging decreases the skin's fl exibility and elasticity, increasing susceptibility to mechanical damage [ 5 ] .…”

Investigation of temperature effect on cell mechanics by optofluidic microchips

“…It is well known that cell mechanics plays an important role in various cellular functions [1][2][3][4], and in many disease-related mutations, especially for carcinogenesis [5]. Besides, it was also demonstrated that cell's mechanical properties can be used as an intrinsic and reliable marker to distinguish between different cell types [6,7].…”