Novel Strategy To Restore Youthful Facial ContourNovember 2015
By Robert Goldfaden and Gary Goldfaden, MD
Over time, the skin’s underlying support structure of collagen and elastin degenerates from repeated sun exposure. Combined with the effects of gravity, these factors rob facial skin of its youthful firmness and resilience.1-3
Medical interventions to improve loose and sagging skin such as surgical face lifts are costly and associated with side effects.4,5 This leaves many people without a viable option.
You may not have to be one of them. Scientists have uncovered several new compounds that can turn the tide in your favor—providing a safe and effective alternative to current treatments.
This article will describe how an innovative peptide and three plant stem cell extracts work together to stimulate new production of collagen and elastin in aging skin, while protecting existing collagen and elastin against damaging ultraviolet radiation (UV). This novel strategy results in visibly firmer, more defined, younger-looking facial skin.
Collagen And Elastin: The Dynamic Duo
The physical appearance of your skin largely depends on the condition of the extracellular matrix that lies between cells in the dermis. In younger skin, the extracellular matrix is a highly organized structure rich in collagen and elastin proteins that work in tandem to maintain firmness and resilience.6,7
Collagen types I and III comprise most of the extracellular matrix, forming rope-like fibers that supply high-tensile strength and resist stretching.8 A different type of collagen—type IV—is a major component of the basement membrane that connects the dermis to the epidermis, where it self-assembles into a scaffolding network to provide mechanical stability.1
Elastin, on the other hand, accounts for the impressive ability of skin to stretch and recoil, allowing it to return to its original shape after facial expressions such as smiling, laughing, and squinting. Although elastin makes up only a small percentage of the total dry weight of the dermis, it is equally as important as collagen in supporting the appearance of youthful skin.9,10
As we age, however, elastin and collagen fibers decrease as a result of reduced synthesis,11,12 as well as increased degradation from UV-induced matrix metalloproteinases which are enzymes that destroy our skin’s support structure.13,14 Combined with the force of gravity, these age-related changes translate into loose and saggy facial skin with fine lines and wrinkles.15
Since surgical face lifts, injections, and laser treatments are expensive, uncomfortable, and often accompanied by side effects,14,15 researchers have been investigating compounds that could lift and tighten loose skin without these notable drawbacks.
Let’s take a look at how a unique peptide regenerates collagen and elastin to deliver remarkable skin tightening effects.
Acetyl Tetrapeptide-2 Creates New Collagen And Elastin
Aware of the fact that collagen and elastin molecules are too large in molecular weight to significantly penetrate the skin,16 scientists designed a low-molecular weight peptide called acetyl tetrapeptide-2 to overcome this problem.17
When scientists treated dermal fibroblasts with acetyl tetrapeptide-2, they observed a 47% increase in type I collagen synthesis.17 In addition, it was shown to favorably modulate gene expression of collagen types I and IV to improve skin cohesion and resistance. 17
Elastin is made from its precursor molecule tropoelastin, which forms elastic fibers after key steps involving the enzyme lysyl oxidase-like 1 (LOXL1) and glycoprotein fibulin-5 (FBLN5).18-20 Both of these compounds decline with advancing age and consequently interfere with the proper formation of elastic fibers that give skin its elasticity.212,22
Acetyl tetrapeptide-2 has not only been shown to increase the synthesis of elastin by 22%, but also encouraged its formation into functional fibers by raising LOXL1 and FBLN5 1.7 fold and 2.3 fold, respectively.17
Additional research shows that acetyl tetrapeptide-2 further supports skin firmness and elasticity by producing adhesion molecules that strengthen the attachment of cells to the extracellular matrix.17
To determine its effectiveness in humans, researchers conducted a clinical trial involving a group of mature women suffering from saggy facial skin. After eight weeks of twice daily applications of acetyl tetrapeptide-2 to the targeted region, participants had average reductions of 9.5% in indentation and 23.2% in a skin flaccidity area parameter—leaving them with noticeably tighter and smoother facial skin.17
Next, we’ll examine plant secondary metabolites and their protective role against sun damage that damages elastin and collagen in the first place.
Targeting Plant Secondary Metabolites
Have you ever wondered why some plants have astonishing life spans? The answer lies in the remarkable regenerative capacity of meristematic cells located in the tips of plant roots and shoots.23,24 These plant stem cells, like human stem cells, can self-renew or differentiate into any other type of cell with a specific function based on the surrounding environment.25
For instance, meristematic cells give rise to secondary metabolites as part of the plant’s survival strategy under stress conditions imposed by living microorganisms (biotic stress) or the physical environment (abiotic stress).26,27 Although once believed to be useless waste products, secondary metabolites have now been shown to demonstrate potent, anti-inflammatory and anti-microbial properties—all of which shield the skin against its external enemies.28,29
Scientists quickly turned to plant cell culture as a means to access secondary metabolites, but early research was unsuccessful.30 After going back to the drawing board, scientists soon discovered a novel way to target secondary metabolites. By co-culturing plant stem cells with microorganisms (like bacteria), biotic stress is created that promotes the formation of secondary metabolites.31-33 More importantly, this approach yields sufficient quantities of these high-value compounds.
Plant Stem Cell Extracts And Their Secondary Metabolites
Researchers have identified three plants around the world—Açaí palm, Quercus alba, and Perilla frutescens—shown to adapt and resist harsh environmental conditions, from droughts to intense UV radiation.31-33 To stimulate production of the compounds responsible for this longevity, cells of each plant were extracted and then co-cultured with bacteria. This resulted in the following plant stem cell extracts, each of which provide a specific secondary metabolite:
- Euterpe oleracea fruit extract (Cabbage Palm Fruit of the açaí palm family)—ferulic acid31
- Perilla frutescens extract—rosmarinic acid32
- Quercus alba bark extract—tannic acid33
The skin’s loss of firmness and flexibility can be traced back to unprotected sun exposure. Plant stem cell extracts and their respective secondary metabolites have been demonstrated in laboratory studies to reduce damage to existing collagen and elastin fibers from ultraviolet radiation in several ways:
- Plant stem cell extracts modulate pro-inflammatory cytokine production following exposure to ultraviolet radiation. For instance, these stem cell extracts decrease the synthesis of a damaging cytokine called interleukin-6 (IL-6).31-33 As people age, IL-6 levels increase, which triggers the release of matrix metalloproteinase ezymes that degrade collagen and elastin.34,35
- They suppress UV-induced free radicals—evident by their high oxygen radical absorbance capacity (ORAC) scores 31-33 that contribute to oxidative stress involved in the destructive cross-linking of healthy collagen and elastin fibers.36 This process renders both proteins dysfunctional, leading to loose and inflexible skin.
- By inhibiting free radical generation, plant stem cell extracts protect vulnerable DNA and preserve the natural order for regenerating new collagen and elastin.31,37
- Ultraviolet radiation alters mitochondrial energy production in dermal fibroblasts, resulting in less energy in the form of adenosine triphosphate (ATP).38 This slows down cellular activities that maintain firm and smooth skin. By ramping up ATP production, plant stem cell extracts replenish energy levels to improve cellular metabolism, promote new collagen and elastin, and boost DNA repair. 31-33
Human studies using the same three plant extracts confirm their ability to increase water content in aging cells, keeping them plump to give the appearance of firmer and smoother skin.31-33 In one of these human studies, Euterpe oleracea fruit extract improved moisture by 51% within 24 hours and 102% after four weeks compared to a control, thereby demonstrating its immediate and long-lasting hydrating effects. 31
While wrinkles and fine lines have been treated successfully with topical solutions, improving loose and sagging skin so far has been a losing battle. One primary reason is that medical interventions are costly, uncomfortable, and often accompanied by side effects.
Fortunately, scientists have identified new compounds that provide a safe and effective alternative to current treatments.
Acetyl tetrapeptide-2 enhances skin cohesion and firmness by triggering new production of collagen and elastin, while three plant stem cell extracts and their respective secondary metabolites work to protect existing collagen and elastin fibers from damaging UV rays.
This novel strategy results in visibly firmer, more defined, younger-looking facial skin.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
- Bernstein EF, Chen YQ, Kopp JB, et al. Long-term sun exposure alters the collagen of the papillary dermis. Comparison of sun-protected and photoaged skin by northern analysis, immunohistochemical staining, and confocal laser scanning microscopy. J Am Acad Dermatol. 1996 Feb;34(2 Pt 1):209-18.
- Suwabe H, Serizawa A, Kajiwara H, et al. Degenerative processes of elastic fibers in sun-protected and sun-exposed skin: immunoelectron microscopic observation of elastin, fibrillin-1, amyloid P component, lysozyme and alpha1-antitrypsin. Pathol Int. 1999 May;49(5):391-402.
- Ohshima H, Tada A, Kanamaru A, et al. Relevance of the directionality of skin elasticity to aging and sagging of the face. Skin Res Technol. 2011 Feb;17(1):101-7.
- Moyer JS, Baker SR. Complications of rhytidectomy. Facial Plast Surg Clin North Am. 2005 Aug;13(3):469-78.
- Haedersdal M. Cutaneous side effects from laser treatment of the skin: skin cancer, scars, wounds, pigmentary changes, and purpura—use of pulsed dye laser, copper vapor laser, and argon laser. Acta Derm Venereol Suppl. 1999;207:1-32.
- Krieg T, Aumailley M. The extracellular matrix of the dermis: flexible structures with dynamic functions. Exp Dermatol. 2011 Aug;20(8):689-95.
- Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. J Cell Sci. 2010 Dec;123:4195-200.
- Lovell CR, Smolenski KA, Duance VC, et al. Type I and III collagen content and fibre distribution in normal human skin during ageing. Br J Dermatol. 1987;117(4):419-28.
- Uitto J, Li Q, Urban Z. The complexity of elastic fiber biogenesis in the skin—a perspective to the clinical heterogeneity of cutis laxa. Exp Dermatol. 2013 Feb;22(2):88-92.
- Oikarinen A. Aging of the skin connective tissue: how to measure the biochemical and mechanical properties of aging dermis. Photodermatol Photoimmunol Photomed. 1994 Apr;10(2):47-52.
- Uitto J. The role of elastin and collagen in cutaneous aging: intrinsic aging versus photoexposure. J Drugs Dermatol. 2008 Feb;7(2 Suppl):s12-6.
- Rossetti D, Kielmanowicz MG, Vigodman S, et al. A novel anti-ageing mechanism for retinol: induction of dermal elastin synthesis and elastin fibre formation. Int J Cosmet Sci. Feb 2011;33(1):62-9.
- Fisher GJ, Datta SC, Talwar HS, et al. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature. Jan 1996;379:335-9.
- Brennan M, Bhatti H, Nerusu K, et al. Matrix metalloproteinase-1 is the collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin. Photochem Photobiol. 2003;78:43-8.
- Ganceviciene R, Liakou AI, Theodoridis A, et al. Skin anti-aging strategies. Dermatolendocrinol. 2012 Jul 1;4(3):308-19.
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- Thomassin L, Werneck CC, Broekelmann TJ, et al. The Pro-regions of lysyl oxidase and lysyl oxidase-like 1 are required for deposition onto elastic fibers. J Biol Chem. 2005 Dec 30;280(52):42848-55.
- Kadoya K, Sasaki T, Kostka G, et al. Fibulin-5 deposition in human skin: decrease with ageing and ultraviolet B exposure and increase in solar elastosis. Br J Dermatol. 2005 Sep;153(3):607-12.
- Langton AK, Sherratt MJ, Griffiths CE, Watson RE. Differential expression of elastic fibre components in intrinsically aged skin. Biogerontology. 2012 Feb;13(1):37-48.
- Hirai M, Ohbayashi T, Horiguchi M, et al. Fibulin-5/DANCE has an elastogenic organizer activity that is abrogated by proteolytic cleavage in vivo. J Cell Biol. 2007 Mar 26;176(7):1061-71.
- Stahl Y, Simon R. Plant stem cell niches. Int J Dev Biol. 2005;49(5-6):479-89.
- Sablowski R. The dynamic plant stem cell niches. Curr Opin Plant Biol. 2007 Dec;10(6):639-44.
- Heidstra R, Sabatini S. Plant and animal stem cells: similar yet different. Nat Rev Mol Cell Biol. 2014 May;15(5):301-12.
- Nascimento NC, Fett-Neto AG. Plant secondary metabolism and challenges in modifying its operation: an overview. Methods Mol Biol. 2010;643:1-13.
- Hussain MS, Fareed S, Ansari S, et al. Current approaches toward production of secondary plant metabolites. J Pharm Bioallied Sci. 2012 Jan;4(1):10-20.
- Hartmann T. From waste products to ecochemicals: fifty years of research of plant secondary metabolism. Phytochemistry. 2007 Nov-Dec;68(22-24):2831-46.
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- Sundararaj KP, Samuvel DJ, Li Y, et al. Interleukin-6 released from fibroblasts is essential for up-regulation of matrix metalloproteinase-1 expression by U937 macrophages in coculture: cross-talking between fibroblasts and U937 macrophages exposed to high glucose. J Biol Chem. 2009 May 15;284(20):13714-24.
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