ABSTRACT
On the other hand, age-related aberrant ECM microenvironment (altered dermal collagen structural and mechanical property) has a signi‡cant impact on dermal ‡broblasts function by reducing attachment to collagen ‡bers, reduced spreading/size and reduced mechanical tension. Therefore, this working model reveals an inherent self-perpetuating positive feedback nature between impaired dermal ‡broblast function and alteration of dermal collagen structural and mechanical environment. Aged dermal ‡broblast weakens the structural integrity and mechanical properties of the dermal ECM. The weakened dermal ECM microenvironment (age-associated dermal ECM microenvironment) provides less resistance to the mechanical forces exerted on it by dermal ‡broblasts, thereby reducing the mechanical tension and cell spreading/size in the ‡broblasts. This reduced mechanical tension and spreading/size in the ‡broblasts results in further impairing dermal ‡broblast function in collagen homeostasis and weakening the structural integrity and mechanical properties of the dermal ECM. The essential positive feedback between impaired dermal ‡broblast function and loss of the integrity of dermal ECM network is consistent with the biology of aging, which is represented by gradual and progressive loss of homeostatic control within tissues.
