This open access review examines what is known of the role of fibroblast growth factors in mechanisms relevant to skin aging, such as loss of collagen and elastin from the extracellular matrix. This type of paper always makes for an interesting read, and fully mapping the cellular metabolism of aging is the right goal from a fundamental science perspective. When it comes to near term intervention in the aging process, this sort of examination is less helpful, however. Yes, growth factor expression levels change in aging skin cells, and that has consequential effects. But this is in and of itself far removed from the underlying causes of degenerative aging. It is itself a consequence and not a cause. The most efficient way forward is to focus on causes, not to try to intervene downstream in the complexities of a disrupted mechanism. If a complicated metal structure is rusting to structural failure, you fix the rust, you don't try to rework the structure. The same principle applies here, alongside the ever important note that effect sizes tend to be small and unreliable in this sort of work.
Growth factors have become an important therapeutic option to avoid aging, because they are responsible for cell differentiation and maturation, being directly correlated with the minimizations of the topical esthetic changes resulting from age advancement. Growth factor proteins are naturally secreted by cells and interact directly or are sequestered by the surrounding extracellular matrix for presentation to cell surface receptors. The introduction of growth factors in certain damaged sites in the body seeking to stimulate regeneration is clinically related to regenerative medicine, where researchers intend to replace or repair damaged cells, tissues, and organs to effectively restore normal function.
Among the existing growth factors, we highlight the fibroblast growth factor (FGF), which induces the synthesis of type 1 collagen and therefore presents a relevant role in the process of skin aging control. Collagen is the protein responsible for the structure, elasticity, and firmness of the skin and it is produced by cells called fibroblasts. During the aging process, the proliferative and metabolic activity of fibroblasts decreases and their functions are impaired, leading to reduction of the synthesis of structural substances such as collagen, elastin, hyaluronic acid, and chondroitin. In addition, decreased levels of growth factors, reduced amount of collagen, abnormal accumulation of elastin, and reduction in the epidermal and dermal thickness were observed during the aging process.
The FGF family members increase the proliferation and activation of fibroblasts by stimulating the accumulation of collagen as well as stimulating endothelial cell division. With the aging process, fibroblasts have their activity diminished and consequently the synthesis and activity of proteins that guarantee elasticity and resistance such as elastin and collagen are also affected. Thus, in aged skin, there is a lower production of collagen by the fibroblasts and a greater action of the enzymes that degrade it. This lack of balance speeds up the aging process. Although the functions of FGFs are well characterized, their mechanisms of action are still not completely clear. It is known that it involves inter- and extracellular signaling pathways that may be related to the RAS-MAP kinases pathways, PI3K-AKT, PLC-γ, or STAT. Therefore, FGF cell signaling involves interactions with multiple cell signaling pathways and complex feedback mechanisms.
Activation of FGF-1 improves skin elasticity and induces the synthesis of collagen and elastin. One study investigated the impact of FGF-1 on skin cells; results showed that recombinant FGF-1 has a strong effect on cellular proliferation of keratinocytes and fibroblasts. FGF-2 reduces and prevents expression lines and wrinkles through the activation of new skin cells and stimulates the proliferation of cells of mesodermal, ectodermal, and endodermal origin, mainly fibroblasts and keratinocytes. Researchers aimed to evaluate an in vivo method for aged skin rejuvenation through direct injection of intradermal FGF-2. The following rejuvenating effects were observed: improvement of skin smoothness, atrophied skin thickness, and improved viscoelasticity. Keratinocyte growth factor (KGF) is a member of the FGF family. While most FGFs influence the proliferation and/or differentiation of various cell types, KGF appears to act specifically on epithelial cells. A study evaluating the ability of KGF to reduce the visible signs of aging. The results showed that eighteen of the twenty subjects experienced significant improvement.