Fibroblast aging: intrinsic and extrinsic factors

Age-related changes and environmental stresses affect all of the cellular elements in the skin, but changes that occur in stromal fibroblasts are particularly important, because it is these cells that maintain the connective tissue of the skin. From the standpoint of maintaining connective tissue, the most important phenotypic changes include a progressive increase in connective tissue damage, mediated by matrix metalloproteinases (MMPs) and a reduction in new collagen synthesis. Intrinsic changes in the aged fibroblast as well as exposure to environmental insults (e.g. ultraviolet radiation) alter the intracellular signaling events that regulate both collagen synthesis and MMP elaboration. Furthermore, as the connective tissue becomes progressively damaged, it eventually becomes a stimulator of reduced fibroblast synthetic function. The result is a downward spiral that ends, if not checked, in the cosmetic and medical consequences that define aged skin.