Hyper - Skin Anti-Aging

SKIN ANTIOXIDANTS:
REDUCING LIPID OXIDATION AND DNA DAMAGE

An essential for beautiful skin is maintaining healthy skin cells and supporting connective tissue, which radiant a glow that is unmistakable sign of health and youth. Cellular aging is characterized by the progressive accumulation of damage at the molecular level. The primary target of preserving healthy skins cells is ensuring that the cell membrane maintains stability and is not affected by molecular damage and destruction by oxidation of the membrane. Breakdown of the cellular membrane affects the survivability and health of the cell.

Skin Aging by Oxidation:

Oxidation caused by free radicals due to normal aging as well as exposure to UV radiation in the skin affects the aging off every skin component including: proteins, lipids, DNA (see below) and mitochondria. Aging skin (both as chronologically older and as photoaged skin), shows the following loss of youthfulness:

          • Significant INCREASE OF OXIDATION and
             DECREASE IN ANTIOXIDATION capacity
             within the skin cells and tissue with age.
          • Lipid free radicals (peroxides) increase in
             activity in the skin with age. The result is a
             further breaking down the cellular membrane
             of the skin. (1) Hence, lipid antioxidants may
             be of particular value in protecting the
             cellular membrane of the skin from aging.
          • DNA in the skin incurs damage, which affects
             the function of the cell, skin stem cells ability 
             to regenerate the skin, the appearance of the
             skin (more aged) and predisposes the skin
             to cancer. 
          • Mitochondria affected by free radicals may
             lead to premature cellular senescence and
             decreasing the number of healthy skin cells. 

HYPER LONGEVITY™ Ingredients:

Tetrahydrocurmin:
Extremely powerful lipid antioxidant, and has been shown to significantly decrease oxidative stress levels in many research studies.

• Tetrahydrocurcumin is a stronger antioxidant than curcumin (which is also a strong antioxidant) (2,3)
• Inhibits lipid oxidation of the skin cellular membrane. 
• Inhibit oxidative stress due to hyperglycemia. Tetrahydrocurcumin significantly increased levels of the cellular antioxidant glutathione, which offered protection against diabetic complications.(5)
• Preserves Mitochondrial Membrane Potential (MMP). Mitochondria is the energy producing organelle within the cell. MMP reflects the integrity of the outer membrane of the mitochondria and is a key indicator of cellular viability. Free radicals can adversely impact the MMP, lose cellular energy production and cause cellular death. (4) Furthermore, while curcumin is considered a very strong antioxidant, tetrahydrocurcumin has been shown to be even stronger. Tetrahydrocurcumin reduces free radical reducing reactive oxygen species and retaining mitochondrial membrane potential.

Olive Polyphenols (Hydroxytyrosol & Verbascoside):

•Hydroxytyrosol and verbascoside are both potent antioxidants, and protect the skin cell and DNA from damage.(6,7)
• Inhibits lipid oxidation. 
• Prevents oxidative stress related to wrinkle formation, skin thinning, and other skin aging features
• Protects against oxidative DNA damage (including UV radiation induced)
• Hydroxytyrosol and verbascoside both activate the Nrf2 transcription factor, which acts as a powerful activator of gene expression for antioxidant enzymes. Aging is associated with lower levels of Nrf2, with the consequence of lower antioxidant gene expression.(8,9)

Alpha Lipoic Acid: Master Antioxidant

• Recycle other antioxidants
• An activator of Nrf2 transcription factor, for increased antioxidant enzyme synthesis.(10)
• Inhibits Lipid Oxidation (11)

Pterostilbene: Gene Activator and Powerful Antioxidant

• Turns “on” genes which increase intracellular antioxidant enzymes. Pterostilbene is an activator of Nrf2 transcription factor. (12,13)
• Inhibit Lipid Oxidation. More biologically active than resveratrol. (13)

FAST DNA REPAIR DNA Repair (of Oxidative Damage) VERBASCOSIDE:
DNA is very susceptible to oxidative damage caused by free radicals. Free radicals attack the DNA structure, and can seriously affect the functioning of the cell (and aging), increase genetic instability, and increase cancer rates.

• Verbascoside- Verbascoside, a unique polyphenol in olive pulp, has been shown to be able to repair DNA as soon as the damage to the DNA occurs (in nano-seconds).

BLOOD SUGAR ACCELERATES SKIN AGING

                                                                                                                              SKIN AGING REFERENCES

• How Sugar Ages Skin: Glycation

Elevated levels of sugar in the blood stream binds to the important proteins in the skin which provides firmness and elasticity. This binding causes damage to the collagen and elastin fibers. The process is termed glycation. Glycated proteins become toxic, inflammatory, non-functional proteins called advanced glycation endproducts (AGEs). AGEs result in a stiffening and loss of skin elasticity. The damaged protein further results in a weakening of the dermal extra-cellular support structure and eventual loss of the collagen and elastin support proteins. Wrinkles and older looking skin is the ultimate result. Decreasing Skin Protein Glycation and AGES formation. In order to decrease the level of glycation and accelerated skin aging, optimal sugar levels should be maintained, including avoidance of sugar spikes.

• Maintaining Optimal Blood Sugar Levels

Hyper Longevity™ helps achieve healthy and more optimal blood sugar levels. Importantly, Hyper Longevity™ ingredients help to reduce skin damaging glycation, through both lowering of blood sugar (and blood sugar spikes) and directly blocking the formation of AGEs.

o Crominex®3+. A highly effective and very safe form of chromium which increases cellular sensitivity to insulin, supporting healthier blood glucose levels.
o Alpha Lipoic Acid. Improves glucose utilization and reduce glycation and advanced glycation end products (AGEs).(8) Research indicates that alpha lipoic acid can also significantly attenuate fructose induced damage to skin collagen caused by glycation.(9)
o Pterostilbene. Blocks AGEs formation. Also supports lowering of blood sugar and improves insulin sensitivity. Enhanced insulin sensitivity is via increasing levels of the hormone adiponectin while decreasing leptin. (7) Pterostilbene also protects the beta cells of the pancreas, which secrete insulin.

• Avoiding Sugar Spikes

Sugar spikes are abnormally high levels of blood sugar that normally occur after a meal or drink. The excessive amounts of sugar in the blood cannot be adequately processed by the body, and the high levels of sugar can damage protein structures throughout the whole body. The youthful firmness and elasticity of the skin is due to the protein in the dermal layer (collagen and elastin). When sugar binds to these skin proteins, they become irreversibly damaged and the skin ages. Grape Seed Extract has been shown to siginificantly lower blood sugar spikes (hyperglycemia)  which occur after a high carbohydrate meal. (15)

• Foods to Avoid

 In addition to avoiding high sugar foods (simple carbohydrates) such as candies, cakes and other desserts, drinks such as sugared sodas (including high fructose corn syrup) and breads should also be avoided. Furthermore, complex carbohydrates, such as potatoes, white rice and pasta also break down quickly and cause sugar spikes.

• Fructose (fruit sugar) - SIgnificant Contributor in Skin Aging

While fructose is a naturally occurring sugar in fruits, and honey, excessive consumption of fructose can also lead to glycation (cross-linking of dermal collagen fibers) and significant aging of the skin. Fructose has a very high glycation forming activity level (higher than glucose). Fruit juices are especially bad, since they are rapidly absorbed in liquid form, creating an instant system overload of fructose in the body. Studies have shown that fructose may be the most destructive sugar for skin aging.

INHIBITING FAT INDUCED AGING OF SKIN 

Increasing levels of fat (adipose) tissue beneath the skin layer can directly impact the health of the dermal layer. Free fatty acids released from underlying fat tissue from enlarged adipocytes DECREASES FIBROBLAST PROLIFERATION. Since fibroblasts play a pivotal role in replenishing the elastic layer of the skin, reduction in fibroblasts reduces the elasticity and fullness of the dermal layer and ages the skin. Research demonmstrates that it is only the ENLARGED ADIPOCTYES which inhibit fibroblast proliferation not the small adipocytes.

Enlarged adipocytes occur due to increased stimulation of genes associated with increased fat production (adipocyte proliferation) and resulting accumulation of fat in the body. DECREASING SKIN ELASTICITY IN OVERWEIGHT AND OBESE INDIVIUALS. In fact, obese individuals do have decreased dermal skin elasticity because of the negative impact of enlarged fat cells. Increased levels of fat accumulation under the dermal layer of skin, has been shown to reduce the ability of the dermal layer to replenish the elastic proteins

HYPER LONGEVTY™ - Ingredients which suppress proliferation and enlargement of adipocytes:

Pterostilbene – Causes an both an INHIBITION of the number of adipocyte cells, and size of adipocytes. Therefore, pterostilbene results in less fat accumulation in adipocyes, resulting in smaller adipocytes. Research demonstrates that it is only the ENLARGED ADIPOCYES which release fatty acids which have a toxic effect on the fibroblasts in the skin. Small adipocytes do not have such an effect.

Hydroxytyrosol  – Prevents adipocyte differentiation (at the early stages of differentiation) thereby reducing adipocyte proliferation and maturation.

          GOLD FOR GORGEOUS™ - Ingredients which suppress proliferation and enlargement of adipocytes:

Curcumin – Has an inhibitory effect on adipose tissue accumulation and an anti-inflammatory effect on the adipocytes.

• HIGH FAT DIETS. Normally, high fat diets result in increased expression of genes which stimulate increased adipocyte differentiation (increasing the number of the fat cells) and fatty accumulation. When curcumin was added to the high fat diet of experimental animals, there was a significant attenuation of the typical increased fatty accumulation in adipose tissue which would be normally observed. Increased gene expression for adipose accumulation (adipogenesis) was suppressed, thereby preventing increased levels of obesity and fat (adipocyte) formation.

• PREVENTING FAT ACCUMULATION. Curcumin’s effect on inhibiting adipogeneis has been observed in research involving both animals(2) and in cell cultures (3). significantly reduced lipid accumulation during the early stages of adipocyte development. Attenuates fatty accumulation under dermal layer of skin. Fatty acids released from adipose tissue have a NEGATIVE EFFECT on the DERML FIBROBLAST layer. This is believed to be the cause of obesity causing decreased elasticity of the dermal layer of the skin. Curcumin inhibits adipocyte accumulation and differentiation, which is responsible for the accumulation of fatty tissue. Therefore, curcumin may have a protective effect on the dermal layer, maintaining skin elasticity with age.

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REFERENCES:

1. Ezure T, et al. Negative regulation of dermal fibroblasts by enlarged adipocytes through release of free fatty acids. J Invest Dermatol. 2011 Oct;131(10):2004-9. doi: 10.1038/jid.2011.145. Epub 2011 Jun 23.

2. Hsu Cl, et al. Inhibitory effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells. Food Funct. 2012 Jan;3(1):49-57.

3. Shao W, et al. Curcumin Prevents High Fat Diet Induced Insulin Resistance and Obesity via Attenuating Lipogenesis in Liver and Inflammatory Pathway in Adipocytes. PLoS One. 2012;7(1):e28784.

4. Ahn J, et al. Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling. Am J Physiol Cell Physiol. 2010 Jun;298(6):C1510-6.

5. Drira R, et al. Oleuropein and hydroxytyrosol inhibit adipocyte differentiation in 3 T3-L1 cells. Life Sci. 2011 Nov 7;89(19-20):708-16.

GENE ACTIVATION: REGULATING GENES TO SLOW AGING
HYPER LONGEVITY™

Slowing Aging: FOXO and Sirtuins (SIRT)

Factors which affect aging are many and complicated. What is known:

• Aging affects the entire body, including the skin. While the skin is the most recognizable sign of aging, simultaneous aging is also taking place internally.
• Genes, those segments of DNA which encode (manufacture) proteins, which affect the functioning of the body, can significantly alter the path of longevity. Sirtuins are the proteins which are produced by activation / expression of a SIRT gene. For example, expression of SIRT1 produces sirtuin 1.

Studies involving worms, mice and fruit flies, which have significantly shorter lifespans, have offered clues into the potential genes and gene activators (transcription factors) involved in the aging process. Transcription factors are the protein activators of genes, which is also termed as gene expression. The expression of a gene creates a gene specific protein which is involved in regulating metabolic pathways in the body, including glucose metabolism, energy homeostasis and longevity. FOXO transcription factors, for example, are expressed in response to specific environmental factors, which in turn activate specific genes.

FOXO (transcription factors) are involved in regulating genes involved in cellular growth and longevity. In studies with lab animals, FOXO has been shown to be a potent longevity extender. It is postulated that FOXO may be the most important gene factors involved in longevity promotion. Additionally, there also appear to be a regulatory relationship between SIRT longevity genes and FOXO transcription factors.

TETRAHYDROCURCUMIN- Regulator of FOXO / Skin Anti-Aging FOXO Activator

• Tetrahydroxycurcumin, a bioactive metabolite of curcumin, regulates oxidative stress and cellular aging by the activating FOXO transcription factors. Laboratory studies support the powerful anti-aging effects of tetrahydrocurcumin.(3)
• Tetrahydroxycurcumin extends the lifespan of lab animals.

o Increased the lifespan of Mice an average of 11.7%(1, 2)
o Increased the lifespan of Drosophila melanogaster (fruit fly) based on FOXO inhibition of oxidative stress (3)

SKIN ANTI-AGING

• Tetrahydroxycurcmin promotes skin health and longevity

o Superb Antioxidant. Protects keratinocytes (skin cells) by the inhibition of superoxideradicals Keratinocytes are the predominant cell type in the outermost layer of skin (epidermis).
o Prevents cellular membrane lipid oxidation. o Anti-Inflammatory: Including inhibition of inflammatory 5-LOX and COX enzymes.
o Inhibits breakdown of connective tissue in skin by inhibiting the enzymes: Inhibits Collagenase (breaks down collagen) Inhibits Hyaluronase (breaks down hyaluronic acid)

• Tetrahydroxycurcumin activating FOXO transcription factors target genes:

o Enhancing DNA Repair o Detoxification of Reactive Oxygen Compounds – by increasing Catalase and MnSOD (Maganese Superoxide Dismutase). Both are enzymes which are powerful in breaking down toxic cell oxygen reactive molecules.

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Sirtuins proteins (Genes SIRT1-7)  regulate biological pathways, including energy metabolism. Calorie restriction, for example, is known to increase longevity. Under conditions of calorie restriction, metabolism pathways activate SIRT1 genes, to produce sirtuin 1 protein. The sirtuin 1 protein activates pathways which conserve energy and promote longevity. Resveratrol is perhaps the most well known SIRT1 gene activator, which is known as the “longevity gene”.

HYDROXYTYROSOL & PTEROSTILBENE – Sirtuin Activators / Skin Anti-Aging Sirtuin Activator

• Hydroxytyrosol - .Olive polyphenol which invokes SIRT1, SIRT3 and SIRT4 anti-aging gene expression and FOXO. (4)

o Promotes longevity via targeted gene expression.
o Enhances mitochondrial biogenesis (new mitochondria) by virtue of SIRT3 and SIRT4 expression.

• Pterostilbene – Invokes expression of the SIRT1 and other SIRT genes. Similar in structure and action as its related molecule resveratrol, but has a significantly longer bioavailability than resveratrol.

SKIN ANTI-AGING

• Hydroxytyrosol – Protects against skin aging by increasing antioxidant levels. Hydroxytyrsol prevents skin aging in the outermost layer of skin, the epidermis and the layer containing the collagen and elastin extracellular martix, the dermis. In the dermal layer, hydroxytyrosol extends the replicative lifespan of the fibroblasts, the cells necessary for the production of connective tissue, collagen and elastic fibers as part of the skin extracellular structural framework.

o Skin fibroblasts synthesize the extracellular matrix in the dermal layer, which acts as the supporting structure for skin. Hydroxytyrosol extends the life of fibroblasts, including their ability to maintain and regenerate connective tissue, collagen and elastin as part of the extracellular matrix.
o Skin fibroblasts are therefore capable replenishing connective tissue, for longer periods of time. Hydroxytyrosol increases levels of antioxidant MnSOD activity thereby reducing mitochondrial oxidative damage.(5) MnSOD is a major free radical scavenger in the skin in both the epidermal kertinocytes and the dermal fibroblasts and helps prevent skin aging.

REFERENCES:

(1) Kitani K, et al. Interventions in aging and age-associated pathologies by means of nutritional approaches. Ann N Y Acad Sci. 2004 Jun;1019:424-6.

(2) Kitani K, et al. The effects of tetrahydrocurcumin and green tea polyphenol on the survival of male C57BL/6 mice. Biogerontology. 2007 Oct;8(5):567-73. Epub 2007 May 22.

(3) Xiang L, et al. Tetrahydrocurcumin extends life span and inhibits the oxidative stress response by regulating the FOXO forkhead transcription factor. Aging (Albany NY). 2011 Dec 8.

(4) Mukherjee S, et al. Expression of the longevity proteins by both red and white wines and their cardioprotective components, resveratrol, tyrosol, and hydroxytyrosol. Free Radic Biol Med. 2009 Mar 1;46(5):573-8.

(5) Sarsour EH, et al. MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan. Age (Dordr). 2011 Mar 8. (6) Sarsour EH, et al. Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts. J Biol Chem. 2005 May 6;280(18):18033-41.