Topical Growth Factors Orchestrate Skin RepairJune 2017
By Robert Goldfaden and Gary Goldfaden, MD
Our skin is under attack on multiple fronts simultaneously.
External factors such as sunlight and air pollution combined with internal factors like advanced glycation end products (AGEs) damage skin tissues. The outward manifestations are wrinkles, fine lines, and pigmentary changes.1-3
Skin has inherent repair processes regulated by dynamic and complex cell-signaling molecules called growth factors.
By activating signaling pathways, growth factors increase cellular and extracellular activity to nourish, rebuild, and remodel the extracellular matrix—the structural framework responsible for skin cohesion, firmness, and elasticity.4-6
In this article, you’ll learn about how replenishing four growth factors that decline with aging can boost natural repair mechanisms, in turn reducing wrinkles, improving elasticity, and restoring moisture to rejuvenate aging skin.
The Natural Skin Repair Process
Our skin is vulnerable to injury from external and internal sources.
Sunlight, smoking, air pollution, and advanced glycation end products (AGEs) generate an overload of free radicals that overwhelm the skin’s network of protective antioxidants.7,8
The resulting oxidative stress increases inflammation and triggers the excessive release of enzymes called matrix metalloproteinases (MMPs) that degrade extracellular matrix components that provide skin integrity and structure.9,10 This damage reduces the rate of skin cell renewal that underlies premature aging.11
Younger skin can repair this damage thanks to unique proteins called growth factors.
In a well-coordinated effort, growth factors communicate with different cell types such as fibroblasts, keratinocytes, and mast cells to perform a variety of cellular activities that enhance skin renewal and repair.12,13 After binding to surface receptors on target cells, growth factors activate signaling pathways involved in cell growth and proliferation,14 decreasing excess tissue inflammation,15 forming new blood vessels,16 and stimulating production of skin matrix components.17,18 Together, these synergistic effects produce new skin cells that maintain tissue homeostasis and delay the signs of aging.
Targeted Growth Factors
Even though the skin produces different growth factors, only a very small minority of them play a crucial role in the healing process.19 Scientists have pinpointed the following four growth factors involved in skin reparative processes:
- Epidermal growth factor (EGF) increases proliferation of epithelial cells to enhance wound healing and activates hyaluronan synthase 2—an enzyme involved in manufacturing hyaluronic acid that restores skin hydration.20-22
- Insulin-like growth factor-1 (IGF-1) stimulates proliferation of fibroblasts that synthesize skin matrix components, including collagen and elastin.23-26
- Vascular endothelial growth factor (VEGF) stimulates the formation of new blood vessels (angiogenesis) and increases vascular permability to allow a greater delivery of oxygen and nutrients into the extracellular matrix to faciliate repair.17,27
- Fibroblast growth factor (FGF) is an important player in the regeneration and proliferation of skin cells.28
In essence, these growth factors work in harmony to nourish and restore the functionality and appearance of the extracellular matrix to help retain healthy, youthful skin. The problem is that as we age, production of growth factors naturally declines.29 As the oxidative damage accumulates, it speeds up the loss of collagen, elastin, and hyaluronic acid that results in dry skin, fine lines, and wrinkles.
Clinical Testing in Humans
Replenishing these natural growth factors has been shown to reduce visible signs of aging.
In a clinical trial performed on twelve women, ages 43-50, participants applied a topical cream of these growth factors, glutamine, and folic acid daily to their facial region for four weeks.
Researchers observed a 46% decrease in wrinkles under the eyes, and a 21% reduction in the appearance of crow’s feet. Skin elasticity improved by 47% and immediate results were noted for moisturization, which increased by 83% just after applying and by 64% at the end of the study.30
Youthful skin reflects the inner workings of growth factors that drive tissue repair and regeneration in response to both internal and external factors. The decreased concentrations of four key growth factors as we grow older contribute to the deterioration of the skin matrix and lead to the telltale signs of aging.
Replenishing these growth factors restores the skin’s natural repair processes. Research shows that when topically applied as a cream, these growth factors produce noticeable effects that result in firmer, younger-looking skin.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
Gary Goldfaden, MD, is a clinical dermatologist and lifetime member of the American Academy of Dermatology. He is the founder of Academy Dermatology in Hollywood, FL, and Cosmesis Skin Care. Dr. Goldfaden is a member of Life Extension®’s Medical Advisory Board. All Cosmesis products are available online.
- Farage MA, Miller KW, Elsner P, et al. Intrinsic and extrinsic factors in skin ageing: a review. Int J Cosmet Sci. 2008;30(2):87-95.
- Farage MA, Miller KW, Elsner P, et al. Functional and physiological characteristics of the aging skin. Aging Clin Exp Res. 2008;20(3):195-200.
- Gkogkolou P, Bohm M. Advanced glycation end products: Key players in skin aging? Dermatoendocrinol. 2012;4(3):259-70.
- Krieg T, Aumailley M. The extracellular matrix of the dermis: flexible structures with dynamic functions. Exp Dermatol. 2011;20(8):689-95.
- Wilgus TA. Growth Factor-Extracellular Matrix Interactions Regulate Wound Repair. Adv Wound Care (New Rochelle). 2012;1(6):249-54.
- Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010;123(Pt 24):4195-200.
- Fisher GJ, Kang S, Varani J, et al. Mechanisms of photoaging and chronological skin aging. Arch Dermatol. 2002;138(11):1462-70.
- Jeanmaire C, Danoux L, Pauly G. Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study. Br J Dermatol. 2001;145(1):10-8.
- Quan T, Qin Z, Xia W, et al. Matrix-degrading metalloproteinases in photoaging. J Investig Dermatol Symp Proc. 2009;14(1):20-4.
- Fagot D, Asselineau D, Bernerd F. Matrix metalloproteinase-1 production observed after solar-simulated radiation exposure is assumed by dermal fibroblasts but involves a paracrine activation through epidermal keratinocytes. Photochem Photobiol. 2004;79(6):499-505.
- Panich U, Sittithumcharee G, Rathviboon N, et al. Ultraviolet Radiation-Induced Skin Aging: The Role of DNA Damage and Oxidative Stress in Epidermal Stem Cell Damage Mediated Skin Aging. Stem Cells Int. 2016;2016:7370642.
- Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev. 2003;83(3):835-70.
- Goldman R. Growth factors and chronic wound healing: past, present, and future. Adv Skin Wound Care. 2004;17(1):24-35.
- Bhora FY, Dunkin BJ, Batzri S, et al. Effect of growth factors on cell proliferation and epithelialization in human skin. J Surg Res. 1995;59(2):236-44.
- Pastore S, Mascia F, Mariani V, et al. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol. 2008;128(6):1365-74.
- Johnson KE, Wilgus TA. Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair. Adv Wound Care (New Rochelle). 2014;3(10):647-61.
- Tran KT, Griffith L, Wells A. Extracellular matrix signaling through growth factor receptors during wound healing. Wound Repair Regen. 2004;12(3):262-8.
- Schultz GS, Wysocki A. Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen. 2009;17(2):153-62.
- Available at: http://emedicine.medscape.com/article/1298196-overview#showall. Accessed March 21, 2017.
- Pienimaki JP, Rilla K, Fulop C, et al. Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem. 2001;276(23):20428-35.
- Cai JL, Li M, Na YQ. Correlation between hyaluronic acid,hyaluronic Acid synthase and human renal clear cell carcinoma. Chin J Cancer Res. 2011;23(1):59-63.
- Hardwicke J, Schmaljohann D, Boyce D, et al. Epidermal growth factor therapy and wound healing--past, present and future perspectives. Surgeon. 2008;6(3):172-7.
- Gartner MH, Benson JD, Caldwell MD. Insulin-like growth factors I and II expression in the healing wound. J Surg Res. 1992;52(4):389-94.
- Svegliati-Baroni G, Ridolfi F, Di Sario A, et al. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology. 1999;29(6):1743-51.
- Mueller RV, Hunt TK, Tokunaga A, et al. The effect of insulinlike growth factor I on wound healing variables and macrophages in rats. Arch Surg. 1994;129(3):262-5.
- Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997;276(5309):75-81.
- Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280(6):C1358-66.
- An JJ, Eum WS, Kwon HS, et al. Protective effects of skin permeable epidermal and fibroblast growth factor against ultraviolet-induced skin damage and human skin wrinkles. J Cosmet Dermatol. 2013;12(4):287-95.
- Sundaram H, Mehta RC, Norine JA, et al. Topically applied physiologically balanced growth factors: a new paradigm of skin rejuvenation. J Drugs Dermatol. 2009;8(5 Suppl Skin Rejuenation):4-13.
- Available at: http://www.independentchemical.com/adminimg/productpdf/15415739261544256163bio-placenta.pdf Accessed March 9, 2017.