Similar, but not identical, modulation of expression of extracellular matrix components during in vitro and in vivo aging of human skin fibroblasts

Abstract

Regulation of the synthesis of procollagen and other extracellular matrix components was examined in human skin fibroblasts obtained from donors of various ages, from fetal to 80 years old (in vivo aged), and in fetal fibroblasts at varying passage levels (in vitro aged). Growth rates and saturation densities of fibroblasts decreased with increasing age of the donor and after passage 20 of fetal fibroblasts. The rates of collagen and proteoglycan synthesis also decreased during both types of aging to about 10-25% of the rate in early passage fetal fibroblasts, whereas the synthesis of total noncollagenous proteins was not greatly affected. Decreased collagen synthesis in both types of aging was correlated with lower steady-state levels of mRNAs for the two subunits of type I procollagen mRNA, although their regulation was not coordinate. Type III collagen mRNA levels also declined in both types of aging. The concentration of fibronectin mRNA also decreased during in vitro aging but more rapidly than the collagen mRNAs, whereas in fibroblasts from 51-80-year-old donors, it was similar to or higher than in early passage fetal fibroblasts. This study suggests that the decreased synthesis of procollagen and proteoglycans in in vivo aged fibroblasts represents changes that are responsible for intrinsic degenerative changes that occur in human skin during aging. Furthermore, although in vitro and in vivo aging were similar in many respects, they were not equivalent, as evidenced by the differences in regulation of fibronectin expression.

Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices

“…Previous studies have demonstrated that age-related modifications are related to cell division, DNA synthesis and cell migration changed by mechanical forces (33,42,43). It has been reported that fibroblast aging is associated with the disruption of cytoskeletal function, such as decreased actin polymerization, which in turn reduces cell elasticity (36,44).…”

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

“…Other sources of cells used in bone tissue engineering include adiposederived stem cells [32] and periosteal cells [40,65]. Human dermal fibroblasts are another attractive source of cells that can meet the criteria for bone tissue engineering [89]. Recent studies have investigated the ability of cells committed to a fibroblastic lineage to undergo osteogenic differentiation.…”

Stiffening of Human Skin Fibroblasts with Age

“…To date, several studies have examined age-related alterations in cell division, biosynthesis (1)(2)(3), and cell migration (4), but there is little information about the relationship between aging and the mechanical properties of cells. Previous studies have shown that biomechanical properties are important for cell functions that are regulated by mechanical forces (5,6).…”

“…Changes in mechanical properties of the skin are generally referred to extracellular aspects such as alterations in polymerization and cross-linking of collagen and elastin (15). In this context, age-related changes have been observed for protein synthesis and production of ECM components (1,16,17). Further, atomic force microscopy studies indicate that individual epithelial cells show a considerable increase in stiffness in vitro at higher passage numbers (18,19).…”