Six Anti-aging Genes and Solutions For Your Skin

Small variations in DNA, called single nucleotide polymorphisms, or SNPs (pronounced “snips”), account for all human genetic differences - including how efficient we are at key biological processes. Here are a few that affect the skin and aging:

• MMP-1 (collagenase) is an enzyme that degrades collagen.
— Collagen is the main protein of connective tissue (cartilage, joints, skin) and the most abundant protein in our bodies.
— Collagen is constantly synthesized and broken down in an ongoing cycle to form new tissue.
— Collagen decrease (age and free radical damage) => imbalance between collagen breakdown and its reformation.
• Premature aging
• Inflammation
• Joint pain
• Increased risk of skin photo-aging.
• SNPs in the MMP-1 gene causes increased rates of collagenase production

MMP1, also known as collagenase, is an enzyme that breaks down collagen. Collagen is a long, fibrous structural protein that gives your skin its strength and elasticity, and is one of the body’s most abundant components, accounting for nearly 80% of the body’s skin, muscle, cartilage, ligaments, tendons, and bone. Collagen is constantly synthesized and broken down in an on-going cycle. Collagen degradation is a major factor in the aging of skin1,2 resulting in wrinkles and a loss of suppleness and elasticity. People with a SNP in the MMP1 gene produce collagenase at an increased rate, which means their bodies may break down collagen faster than they can rebuild it.3,4 To make matters worse for the skin, the MMP-1 enzyme is also induced by exposure to sunlight and production increases as a function of age.5 These individuals will likely benefit from added support for collagen-rich structures such as the bones and joints.

MMP-1 SNP nutritional support provides a combination of ingredients that strengthen collagen as well as protect it against free radical damage.

Tomato Powder (Lycopene)
— Lycopene quenches singlet-oxygen resulting from direct absorption of UV radiation. Singlet oxygen causes free radical damage to the collagen in the skin.
— Research suggests that reduced lycopene concentrations in the skin => higher risk for sunlight induced skin damage.
— Clinical trial reported daily supplementation with lycopene-containing tomato paste for 10 weeks resulted in 40% less artificially-induced sunburn than the control group.
Grape Seed Extract (Polyphenols/OPCs)
— OPCs protect and stabilize collagen by increasing the cross-linkage of collagen fibril.
— Polyphenols prevent excessive cross-linking which leads to stiff, brittle collagen tissue.
— Multiple small exposures to UV leads to sustained elevations of collagenase and OPCs inhibit the activity of collagenase.
White Tea Extract (Polyphenols, Catechins)
— Catechin- and EGCG-treated collagen exhibited significant resistance against collagenolytic hydrolysis by collagenase and directly inhibits collagenase activity.
— EGCG hampers UV-B-induced MMP-1 production and may be a potential agent for the prevention and treatment of skin photo-aging.
— Supplements containing a combination of extracts from white tea, grape seed and tomato showed significant improvement in the condition, structure and firmness of the skin of post-menopausal women based on several measurable parameters of skin aging.

1 Fligiel S.E.G., at al. Collagen degradation in aged/photoaged skin in vivo and after exposure to MMP-1 in vitro. J Invest Dermatol. 2003. 120:842-848.
2 Varani, J., et al. Decreased Collagen Production in Chronologically Aged Skin. American Journal of Pathology. 2006. 168:1861-1868.
3Cunnane G et al. Early joint erosions and serum levels of matrix metalloproteinase 1, matrix metalloproteinase 3, and tissue inhibitor of metalloproteinases 1 in rheumatoid arthritis. Arthritis Rheum 2001;44:2263-2274.
4 Dörr S et al. Association of a specific haplotype across the genes MMP1 and MMP3 with radiographic joint destruction in rheumatoid arthritis. Arthritis Res Ther 2004;6(3):R199-207.
5 Dong K.K., et al. UV-induced DNA damage initiates release of MMP-1 in human skin. Exp Dermatol. 2008. 17(12):1037-44.

• The Superoxide radical is one of the main free radicals found in the cell and is extremely biologically toxic to cellular DNA and cell machinery.
— Premature aging
— Breast cancer
— Age-related macular degeneration (AMD)
— Prostate cancer
• SOD2 gene encodes for Superoxide Dismutase (SOD), is an antioxidant enzyme which helps neutralize these radicals.
• SNPs on the SOD2 gene can lead to a damaging build-up of the superoxide radicals.

The main function of the superoxide dismutate-2 (SOD2) enzyme is to quench one particularly toxic type of free radical called the superoxide anion.6 Since the superoxide radical is produced in abundance in all cells, it is the starting point for the free radical chain of production. SOD2 has the distinction of being the only enzyme in the mitochondria that can neutralize superoxide.7 Individuals with a SNP in this gene therefore, have a weak first line of defense against free radicals.

This superoxide radical is generated in skin cells when exposed to ultra violet radiation from the sun.8 In addition, superoxide radicals are produced by skin cells that are infected with Propionibacterium acnes, the bacterium that causes acne.9 The presence of SOD2 in the epidermis acts as a selective scavenger for inactivating superoxide and protects skin proteins such as elastin and collagen from harmful effects of sun exposure10and from inflammation caused by acne.9 Individuals with an SNP in the SOD2 gene have a weak first line of defense against superoxide radical attack on the skin. Research suggests that topical application of superoxide-scavenging antioxidants may have an effect on UVB-induced skin photodamage.11SOD2 SNP nutritional support provides antioxidant ingredients with specific activity against the superoxide radical

Green Tea and White Tea Extracts (Polyphenols, Catechins)
— The potent antioxidant activity of these teas has been supported epidemiological studies, cellular research and animal studies.
— Tea catechins have shown direct scavenging activity against superoxide radicals.
— Epigallocatechin-3-gallate (EGCG) was shown to specifically augment the activity of superoxide dismutase, as well as reduce oxidative stress in animal studies.
— Enhancement of superoxide dismutase activity combined with reduction of superoxide radical concentration was seen in heart tissue of animals supplemented with tea catechins.
Bilberry Extract (Anthocyanins)
— Anthocyanins found in bilberry have known superoxide scavenging activity.
— Bilberry extracts have been indicated in the prevention of age-related macular degeneration (AMD) and cataract formation in animal studies.
— Spirulina contains a relatively high level of superoxide dismutase.
— Phycocyanin, the main plant pigment found in spirulina, has been shown to significantly decrease cardiac production of the superoxide anion in animal studies.
Niacin (Vitamin B3)
— Nicotinamide, a derivative of niacin, is required by the body for the production of certain coenzymes essential for proper functioning of superoxide dismutase.

6 Robinson BH. The role of manganese superoxide dismutase in health and disease. J Inherit Metab Dis 1998;21:598-603.
7 Bandy B and AJ Davison. Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med 1990;8:523-39.
8 Pathak M.A. Intrinsic Photoprotection in Human Skin. In: Physicians Guide to Sunscreens. Edited by Lowe N.J. New York, NY. Marcel Dekker. 43.
9 Grange P.A. Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin. PLoS Pathogens. 2009. 5(7). 1-13.
10 Varani, J., et al. Decreased Collagen Production in Chronologically Aged Skin. American Journal of Pathology. 2006. 168:1861-1868.
11 Bissett D.L., et al. Photoprotective effect of superoxide-scavenging antioxidants against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Photodermatol Photoimmunol Photomed. 1990. (2):56-62.

• GPX1 is the most abundant antioxidant enzyme in the Glutathione Peroxidase family with specific activity against hydrogen peroxide.
— Coverts dangerous hydrogen peroxide molecules into water.
— Plays important roles in DNA synthesis and repair, metabolism of toxins, and immune system enhancement.
— Contains selenium in its protein structure and therefore how much GPX1 a person produces is dependent on their selenium levels.
• A SNP on the GPX1 gene can reduce a person’s ability to utilize selenium.

The GPX1 antioxidant enzyme is one the most important antioxidant enzyme in humans. GPX1 specifically detoxifies hydrogen peroxide, an active oxygen species naturally produced in all organisms as a byproduct of metabolism. Hydrogen peroxide plays a major role in both chronological and photoaging of the skin because it is generated from nearly all sources of oxidative stress.12 Like many free radicals, hydrogen peroxide is produced in the skin during exposure to sunlight. Also, hydrogen peroxide is produced upon stimulation by Propionibacterium acnes, the bacterium that causes acne.13 Lowered GPX activity has also been found in individuals affected with psorisasis.14 Individuals with an SNP on the GPX1 gene may have reduced function in quenching hydrogen peroxide in skin cells.

GPX1 is a selenoprotein, meaning it incorporates selenium into its protein structure.15Therefore, how much GPX1 a person produces is dependent on his or her selenium level.16 A SNP on the GPX1 gene can reduce a person’s ability to utilize selenium.17,18That means higher than normal selenium intake is needed to afford protection to hydrogen peroxide-sensitive tissues, particularly lung xvi, xvii and breast tissues.18GPX1 SNP nutritional support provides extra selenium with other ingredients that protect the body against hydrogen peroxide damage and/or increase glutathione peroxidase activity.

— Citrus Bioflavonoids (Naringin, Hesperidin)
• Naringin has been shown to suppress DNA damage induced by hydrogen peroxide.
• Hesperidin has been shown to protect against the damaging effects of hydrogen peroxide.
— Ginkgo leaf, Astragulus Root
• Specific activity against hydrogen peroxide-induced lipid peroxidation and cell death.
— Milk Thistle
• Silymarin reduces oxidative stress caused by hydrogen peroxide as well as increases the antioxidant activity of various antioxidant enzymes including GPX1.
— Anthocyanins (from blueberries, black currants, and grapes)
• Enormous amount of research confirming antioxidant activity of anthocyanins. These include protection against cardiovascular disorders, advancing age-induced oxidative stress, inflammatory responses, and other degenerative diseases.
Turmeric Extract (Curcumin)
— Dietary curcumin was shown to enhance serum GPX activity and lower blood lipid peroxide levels in animals.
Alpha Lipoic Acid
— Animal studies have shown that dietary alpha lipoic acid supplementation increases GPX activity.

12 Chaudhuri, R., Hydrogen Peroxide and Skin Aging. Cosmetic Science, January 2008.
13 Grange P.A. Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin. PLoS Pathogens. 2009. 5(7). 1-13.
14 Wozniak A., et al. Oxidant-antioxidant balance in patients with psoriasis. Med Sci Monit. 2007. 13(1). CR30-33.
15 Bandy B and AJ Davison. Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med 1990; 8:523-39.
16 Rayman MP. Selenium in cancer prevention: a review of the evidence and mechanism of action. P roc Nutr Soc 2005 Nov;64 (4):527-42.
17 Hu YJ and AM Diamond. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res 2003; 63(12):3347-51.
18Hu Y et al. Allelic loss of the gene for the GPX1 selenium-containing protein is a common event in cancer. J Nutr 2005; 135(12 Suppl):3021S-3024S.

• Human microsomal Epoxide Hydrolase (EPHX) is a phase-I xenobiotic metabolizing enzyme that detoxifies potentially toxic epoxides. Xenobiotics are foreign substances (e.g. pollutants, drugs).
• Majority of detoxification mechanisms takes place in the liver.
• Epoxides are also highly reactive and mutagenic leading to certain cancers
• Poorly performing detoxification system leads to:
— Fatigue
— Loss of appetite
— Skin problems
— Premature aging

Epoxides are toxic, highly reactive foreign chemicals present in cigarette smoke, car exhaust, charcoal-grilled meat, smoke from wood burning, pesticides, and alcohol. The body's way of dealing with epoxides is through the enzyme microsomal EPHX, which detoxifies these foreign compounds. In the skin, epoxide hydrolase may play an important part in preventing the systemic absorption of epoxides formed within the epidermis, as well as determining the toxicity of foreign compounds within the skin.19 Due to a SNP on the EPHX gene, people with lowered EPHX activity will have difficulty detoxifying harmful substances and thus be particularly vulnerable to their effects.20EPHX SNP nutritional support that increases activity of the EPHX enzyme along with ingredients to support and enhance all of the natural mechanisms the liver uses to detoxify.

Green Tea Extract (Polyphenols, Catechins)
— Green tea consumption is correlated with fewer disorders of the liver and certain cancers caused by environmental xenobiotics.
— in vitro studies have shown that green tea extract resulted in dramatic increase in the gene expression for EPHX.
Thistle Family
— Milk Thistle Extract (Silymarin)
• Strong liver antioxidant.
• Increases synthesis of glutathione (an essential element for detoxification and optimal immune function).
• Animal studies have shown it provides good defense against various toxic models of experimental liver diseases.
— Artichoke Extract (Phenolic compounds)
• Exerts a major effect on bile flow and liver protection. Bile is a fluid secreted by the liver and required for the removal of toxic chemicals and metabolites.
Cruceriferous vegetables
— Broccoli and Kale (Indole-3-carbinols, Sulphoraphane)
• Stimulate detoxification enzymes.
• Sulforaphane activates phase II detoxification enzymes in the liver and has strong anti-cancer properties.

19 O’Neill V.A., et al. Epoxide hydrolase activity in human skin. British Journal of Clinical Pharmacology. 1981. 12:517-521.
20 Morisseau C and BD Hammock. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol. 2005;45:311-33

• Tumor Necrosis Factor-α (TNF-α ) is a chemical messenger which mobilizes white blood cells to fight infections and other invaders.
• Unbalanced immune response leads to TNF-α build up resulting in excessive and uncontrolled inflammation.
— Atherosclerosis
— Arthritis
— Cancer
— Heart Disease
— Diabetes
— Alzheimer’s Disease
• SNPs on the TNF-α gene may result in an over-reactive inflammatory response.

Inflammation is a response of the immune system to a perceived attack. While it is a helpful response in the short-term, if inflammation continues unabated, it can negatively affect the cells, tissues, and ultimately, the organs. TNF-α is a cytokine (a chemical messenger of the immune system) that plays a role in inflammatory processes. Overproduction of TNF-α has been implicated in a variety of inflammatory and autoimmune diseases. TNF-α has been found at elevated levels in patients with psoriasis,21 acne,22,23 and other inflammatory skin diseases.24 In addition, toxins and UV light are also potent inducers of TNF-α release from keratinocytes,25 the epithelial cells that comprise skin. Individuals with a SNP on the TNF-α gene may have an over-reactive inflammation mechanism, which can negatively affect the joints,26 brain,27 lungs,28 heart,29 and have also been shown to have a predisposition to acne.23TNF-α SNP nutritional support provides antioxidants that fight the increased production of free radicals caused by aging and antioxidants that specifically regulate TNF-α levels.

Polyphenols from Green Tea, Grape Seed and Pomegranate Extracts
— Increased polyphenol consumption has been linked with preventing numerous diseases associated with aging such as heart disease, cancer, and diabetes.
• Green Tea polyphenols reduced the expression of TNF-α in both in vitro studies and animal studies.
• Polyphenols in pomegranate were shown to modulate inflammatory cell signaling in colon cancer cells by suppressing TNF-α induction of various inflammatory proteins.
• Polyphenol compounds in grape seed extract (OPCs) have a potent inhibitory effect on the expression of the vascular cell adhesion molecule-1 gene, (VCAM-1) which is induced by TNF-α.VCAM-promotes the adhesion of immune response blood cells to endothelial cells, which in turns plays a critical role in the initiation and development of vascular inflammation.
Milk Thistle Extract (Silymarin)
— Silymarin has been shown to block TNF-α induced activation of NF-ĸB, a protein complex regulating the immune response.
— Silymarin also suppressed TNF-α induced production of reactive oxygen species and lipid peroxidation.
— Animal studies have also shown Silymarin inhibits of TNF-α gene expression.

21 BioDrugs.;19(1):47-57.LinksTNF alpha inhibitors in the treatment of psoriasis and psoriatic arthritis. Tobin AM,
22 Guttman, C. Acne pathogenesis. Dermatology Times. 2008.
23Baz K. Association between tumor necrosis factor-alpha gene promoter polymorphism at position -308 and acne in Turkish patients. Arch Dermatol Res. 2008. 300(7):371-6.
24 de Rie M.A. and Bos J.D. Biological Treatment of Immune-Mediated Skin Deases. In: Skin Immune System: Cutaneous Immunlogy and Clinical Immundermatology. Editor: Boss J.D. 2004. Boca Raton, FL. CRC Press. p. 800.
25 Steinhoff M. and Luger T.A. The Skin Cytokine Network. In: Skin Immune System: Cutaneous Immunlogy and Clinical Immundermatology. Editor: Boss J.D. 2004. Boca Raton, FL. CRC Press. P. 353.
26 Lee et al. Tumor necrosis factor-alpha promoter -308 A/G polymorphism and rheumatoid arthritis susceptibility: a metaanalysis. J Rheumatol. 2007;34(1):43-9.
27 Alvarez V et al. Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease. Am J Med Genet. 2002;114(5):574-7.
28 Witte JS et al. Relation between tumour necrosis factor polymorphism TNFalpha-308 and risk of asthma. Eur J Hum Genet. 2002;10(1):82-5.
29 Elahi MM et al. A variant of position -308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease. Heart Lung Circ. 2007 Jun 18;

Free radicals are considered by many scientists to be involved in the aging process. The coenzyme Q10 reductase (NQO1) enzyme converts coenzyme Q10 (ubiquinone) to its reduced form, ubiquinol, which scavenges free radicals in the mitochondria and lipid membranes.30 Some individuals have a SNP in the NQO1 gene that slows the reduction of ubiquinone to ubiquinol, resulting in very low blood levels of this key antioxidant. Consequently, people with this SNP are at high risk of free radical attack.31 Because NQO1 is also involved in the detoxification of compounds foreign to the body, a SNP in the NQO1 gene may cause aberrant cellular changes. CoQ10-depleted skin tissue may be particularly more prone to the damage by free radicals because of its constant exposure environmental oxidants such as sunlight and pollution. CoQ10 positively influences the age-affected cellular metabolism in the skin and enables it to combat signs of aging starting at the cellular level.32 Research has shown that CoQ10 may inhibit the production of epidermal cell interleukin-6, which stimulates fibroblasts in the dermis and contributes to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin.3330 Hosoe K et al. Study on safety and bioavailability of ubiquinol (Kaneka QH) after single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol. 2007;47(1):19-28.
31 Ross D et al. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem Biol Interact. 2000 Dec 1;129(1-2):77-97.
32 Prahl S., et al. Aging skin is functionally anaerobic: importance of coenzyme Q10 for anti aging skin care. Biofactors. 2008. 32(1-4):245-55.
33 Inui M., et al .Biofactors. Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivo. 2008. 32(1-4):237-43.

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