Life Extension Magazine®
Cosmetic procedures like topical fillers and laser resurfacing are established interventions for smoothing out wrinkles and fine lines.
But they can also have side effects that include pigmentation changes, infections, red patches, and bruising.1-3
Hyaluronic acid protects and regenerates the skin’s underlying architecture by increasing moisture,4 stimulating collagen and elastin synthesis,5,6 promoting tissue repair,7-10 and combating ultraviolet radiation.11
Replenishing depleted hyaluronic acid levels can help faciliate a more youthful appearance.
Clinical data show that a topical blend of high and low molecular weight hyaluronic acid rehydrates, smoothes, and rejuvenates aged skin.
What you need to know
- Hyaluronic acid is one of the main components of the extracellular matrix that provides structural support and cohesion to skin.
- Well-known for its hydrating properties, hyaluronic acid also instructs cell behavior to protect and rebuild the extracellular matrix.
- The natural decline in hyaluronic acid as we age is exacerbated by its increased loss from external factors, particularly ultraviolet radiation, leading to wrinkles and fine lines accompanied by dry and saggy skin.
- Fortunately, topical preparations containing both high and low molecular weight hyaluronic acid have been shown to restore healthy texture and hydration to aging skin, while reducing wrinkles and fine lines, to provide a more youthful appearance.
- Topical hyaluronic acid provides the same skin rejuvenation benefits as established topical fillers and laser resurfacing but without the potential pitfalls.
Hyaluronic Acid: The Skin’s Internal Moisturizer
Hyaluronic acid is found throughout most tissues in the body, with the greatest concentration in the skin.12
It has an unmatched capacity to attract and retain up to 1,000 times its weight in water.
Hyaluronic acid forms the extracellular matrix, a loose hydrated network that provides structural integrity and cohesion to skin.13,14
Hyaluronic acid has been a mainstay ingredient of skin care products for decades, and for good reason. It bathes structural proteins collagen and elastin, allowing them to impart mechanical strength and elasticity that keeps skin firm and flexible.
By providing moisture between cells, hyaluronic acid increases volume and fullness that diminishes the appearance of wrinkles and fine lines.
While historically viewed as simply a “space filler,” accumulating research indicates that hyaluronic acid plays a greater role in fighting skin aging than previously thought.
Additional Effects of Hyaluronic Acid
Scientists have discovered that hyaluronic acid triggers a number of dynamic processes in the skin through its interaction with receptor CD44. After binding to the receptor, hyaluronic acid has been shown to:
- Promote cell growth and proliferation to produce new skin cells that have a fresh, more radiant appearance.15,16
- Enhance the formation of new blood vessels (angiogenesis) to transport essential nutrients to skin cells from the bloodstream, thereby providing an ideal environment for tissue repair, healing, and growth.16,17
- Modulate the inflammatory and immune response to ultraviolet radiation, which reduces free radicals that lead to DNA damage and lipid peroxidation.11,18
- Stimulate fibroblasts to produce new collagen by causing mechanical stretching of the dermis.19,20
So, by stimulating cells to protect and remodel the extracellular matrix from external factors—like ultraviolet radiation—hyaluronic acid is one of the most potent weapons for preserving youthful skin.
Skin-Aging Effects of Declining Hyaluronic Acid Levels
The natural decline in hyaluronic acid production as we age is exacerbated by environmental stress, particularly chronic sun exposure.21-24 The fallout is a loss of moisture, abnormal structural changes to collagen and elastin, slowed cell turnover, impaired tissue healing, and compromised photoprotection—all of which lead to skin wrinkling, dryness, and sagging characteristic of premature aging.
Different Molecular Weights of Hyaluronic Acid
The effects of topical hyaluronic acid depend upon its size or molecular weight. High molecular weight hyaluronic acid has been shown to exhibit anti-inflammatory activity on the skin’s surface,25,26 while low molecular weight hyaluronic acid penetrates more deeply into the skin where it boosts hydration and tissue repair.27
Thus, topical preparations containing both are ideal to achieve the complete anti-aging effects of hyaluronic acid.
Let’s now examine research that implemented both forms of hyaluronic acid to safely rehydrate and rejuvenate aged skin.
Effectiveness of Topical Hyaluronic Acid
In a double-blind, randomized, placebo-controlled study, 76 participants between the ages 30 and 60 with crow’s feet applied either a topical cream with a mixture of high and low molecular weights hyaluronic acid or a placebo twice daily to the target area for two months.
Compared to the placebo group, participants treated with hyaluronic acid experienced significant reductions in wrinkle depth and roughness while improving skin hydration and elasticity.28
In another randomized trial, scientists studied 40 healthy subjects with mild-to-moderate clinical signs of facial aging. Participants applied a topical preparation containing a mixture of high and low molecular weight hyaluronic acid or a placebo to the target region for 30 days.
The hyaluronic acid treatment group showed greater reductions in wrinkle depth and volume accompanied by less skin sagginess and more cheekbone volume compared to the placebo group.29
Summary
Hyaluronic acid protects, nourishes, and rebuilds the extracellular matrix responsible for skin cohesion, firmness, and elasticity.
Replenishing depleted levels of hyaluronic acid as we age helps restore healthy, vibrant, and youthful-looking skin.
Research shows that when applied topically, the combination of high and low molecular weight hyaluronic acid is a safer, more affordable alternative to topical fillers and laser resurfacing with similar skin rejuvenation effects.
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.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Advisor at 1-866-864-3027.
References
- Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013;6:295-316.
- De Boulle K. Management of complications after implantation of fillers. J Cosmet Dermatol. 2004;3(1):2-15.
- Shah S, Alam M. Laser resurfacing pearls. Semin Plast Surg. 2012;26(3):131-6.
- Masson F. [Skin hydration and hyaluronic acid]. Ann Dermatol Venereol. 2010;137 Suppl 1:S23-5.
- McKee CM, Penno MB, Cowman M, et al. Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. J Clin Invest. 1996;98(10):2403-13.
- Beasley KL, Weiss MA, Weiss RA. Hyaluronic acid fillers: a comprehensive review. Facial Plast Surg. 2009;25(2):86-94.
- Teriete P, Banerji S, Noble M, et al. Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44. Mol Cell. 2004;13(4):483-96.
- Wang Y, Lauer ME, Anand S, et al. Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress. J Biol Chem. 2014;289(46):32253-65.
- Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol. 2007;23:435-61.
- Noble PW. Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biol. 2002;21(1):25-9.
- Hasova M, Crhak T, Safrankova B, et al. Hyaluronan minimizes effects of UV irradiation on human keratinocytes. Arch Dermatol Res. 2011;303(4):277-84.
- Reed RK, Lilja K, Laurent TC. Hyaluronan in the rat with special reference to the skin. Acta Physiol Scand. 1988;134(3):405-11.
- Nusgens BV. Hyaluronic acid and extracellular matrix: a primitive molecule? Ann Dermatol Venereol. 2010;137 Suppl 1:S3-8.
- John HE, Price RD. Perspectives in the selection of hyaluronic acid fillers for facial wrinkles and aging skin. Patient Prefer Adherence. 2009;3:225-30.
- Kage M, Tokudome Y, Matsunaga Y, et al. Effect of hyaluronan tetrasaccharides on epidermal differentiation in normal human epidermal keratinocytes. Int J Cosmet Sci. 2014;36(1):109-15.
- Park D, Kim Y, Kim H, et al. Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFbeta receptor interaction via CD44-PKCdelta. Mol Cells. 2012;33(6):563-74.
- Slevin M, Krupinski J, Gaffney J, et al. Hyaluronan-mediated angiogenesis in vascular disease: uncovering RHAMM and CD44 receptor signaling pathways. Matrix Biol. 2007;26(1):58-68.
- Li JM, Chou HC, Wang SH, et al. Hyaluronic acid-dependent protection against UVB-damaged human corneal cells. Environ Mol Mutagen. 2013;54(6):429-49.
- Wang F, Garza LA, Kang S, et al. In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin. Arch Dermatol. 2007;143(2):155-63.
- Quan T, Wang F, Shao Y, et al. Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo. J Invest Dermatol. 2013;133(3):658-67.
- Rock K, Grandoch M, Majora M, et al. Collagen fragments inhibit hyaluronan synthesis in skin fibroblasts in response to ultraviolet B (UVB): new insights into mechanisms of matrix remodeling. J Biol Chem. 2011;286(20):18268-76.
- Matuoka K, Hasegawa N, Namba M, et al. A decrease in hyaluronic acid synthesis by aging human fibroblasts leading to heparan sulfate enrichment and growth reduction. Aging (Milano). 1989;1(1):47-54.
- Ghersetich I, Lotti T, Campanile G, et al. Hyaluronic acid in cutaneous intrinsic aging. Int J Dermatol. 1994;33(2):119-22.
- Dai G, Freudenberger T, Zipper P, et al. Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. Am J Pathol. 2007;171(5):1451-61.
- Litwiniuk M, Krejner A, Speyrer MS, et al. Hyaluronic Acid in Inflammation and Tissue Regeneration. Wounds. 2016;28(3):78-88.
- Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med. 1997;242(1):27-33.
- Essendoubi M, Gobinet C, Reynaud R, et al. Human skin penetration of hyaluronic acid of different molecular weights as probed by Raman spectroscopy. Skin Res Technol. 2016;22(1):55-62.
- Pavicic T, Gauglitz GG, Lersch P, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol. 2011;10(9):990-1000.
- Nobile V, Buonocore D, Michelotti A, et al. Anti-aging and filling efficacy of six types hyaluronic acid based dermo-cosmetic treatment: double blind, randomized clinical trial of efficacy and safety. J Cosmet Dermatol. 2014;13(4):277-87.