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PURPLE LONGEVITY® - Rich purple Anthocyanins, Activating Longevity Genes Autophagy and Increasing Glutathione

Boosting longevity is a function of many different attributes. Key among these are activating longevity genes (SIRT1 and FOXO) and decreasing levels of oxidative stress. 

ACTIVATING LONGEVITY GENES -

• Resveratrol and Pterostilbene  - Act as antiaging gene activators, including SIRT1 gene activator.(1)
• Resveratrol and Pterostilbene are correlated with longevity.
• Lingonberry (Lowbush Cranberry) contains powerful anthocyanins which activate FOXO longevity genes. (2)
• Lingonberry may have beneficial effects on obesity health issues, including high fat diet cholesterol, glucose and inflammation.(3)

BILBERRY ANTHOCYANINS (Blue Color)

• Significant increases antioxidant capacity and induction of autophagy (4)
• AUTOPHAGY promotes health and longevity.
• AUTOPHAGY - invoked through increased AMPK and reduced mTOR
• AUTOPHAGY further enhanced intestinal epithelial barrier

 GRAPE SEED EXTRACT (GSE) (5-8)

• GSE grape seeds are anti-oxidative, anti-inflammatory and anti-tumor
• Vascular protective. Including blood pressure-lowering effect in hypertensive research animals. 
• Cardio protective properties, especially against cardiac dysfunction after myocardial infarction.
• Offers protection against ischemic stroke, by reducing oxidative stress levels.
• Is a natural aromatase inhibitor, an enzyme involved with converting androgens (testosterone) to estrogen. 

N-ACETYLCYSTEINE (GLUTATHIONE BOOSTER) (9-11)

• Is a precursor to glutathione. Decreases in glutathione are correlated with aging. Levels of cellular glutathione are predictive of longevity. 
• Improved experimental organisms health and longevity. Increased longevity corresponds to Increased levels of antioxidant enzymes (Catalase and Glutathione)
• Supports restoration of intestinal barrier.
• May be effective against cardiovascular events by increasing intracellular glutathione levels. Glutathione reduces  inflammatory IL-1β, which can can promote atherogenesis

 PURPLE LONGEVITY®  

=> (RESVERATROL | PTEROSTILBENE | LINGONBERRY)

REFERENCES:

(1) Li Y, et al. Effect of resveratrol and pterostilbene on aging and longevity. Biofactors. 2018 Jan.

(2) Scerbak C, et al. Lowbush cranberry acts through DAF-16/FOXO signaling to promote increased lifespan and axon branching in aging posterior touch receptor neurons. Geroscience. 2018 Apr.

(3) Ryyti R, et al. Beneficial effects of lingonberry (Vaccinium vitis-idaea L.) supplementation on metabolic and inflammatory adverse effects induced by high-fat diet in a mouse model of obesity. PLoS One. 2020 May.

(4) Li J, et al. Reduction of Aging-Induced Oxidative Stress and Activation of Autophagy by Bilberry Anthocyanin Supplementation via the AMPK-mTOR Signaling Pathway in Aged Female Rats.  J Agric Food Chem. 2019 Jul.

(5) Mas-Capdevila A, et al. Changes in arterial blood pressure caused by long-term administration of grape seed proanthocyanidins in rats with established hypertension. Food Funct. 2020 Oct.

(6) Ruan Y, et al. Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice. Front Pharmacol. 2020 Dec. 

(7) Kadri S, et al. Protective effect of grape seed extract and orlistat co-treatment against stroke: Effect on oxidative stress and energy failure. Biomed Pharmacother. 2021  Apr.

(8) Kijima K, et al. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006 Jun.

(9) Niraula P, et al. N-Acetylcysteine extends lifespan of Drosophila via modulating ROS scavenger gene expression. Biogerontology. 2019 Aug.

(10) McCarty M, et al. Perspective: Prospects for Nutraceutical Support of Intestinal Barrier Function. Adv Nutr. 2021 Mar.

(11) DiNicolantonio J, et al. Supplemental N-acetylcysteine and other measures that boost intracellular glutathione can downregulate interleukin-1β signalling: a potential strategy for preventing cardiovascular events? Open Heart. 2017 Jul.

Lycium Barbarum - for Vision (Retina) | Longevity | Intestinal Health and Slows Aging!

Lycium Barbarum (LB), also known as wolfberry, has been shown to provide powerful anti-aging effects. Significantly, long term feeding of LB in lab animals have shown increased longevity, eye (retina) support, including age-related macular degeneration (AMD), support liver health and boost of intestinal health and immunity.(1)

  INCREASING MEAN LIFESPAN

• Studies involving D. melanogaster (fruit fly), shown LB increases serum and organ levels of superoxide dismutase (SOD), reduced glutathione and catalase (CAT) antioxidant activity. SOD and CAT have been shown in research models to promote longevity. (2)
• Positively promotes anti-aging pathways (MAPK, TOR, S6K) and increases expression of longevity genes (2)

PRESERVING RETINA FUNCTION

• Retinal diseases have underlying high levels of oxidative stress. Photoreceptors and RPE (Retinal Pigment Endothelium) have very high metabolic activity and additional stress comes from photooxidative damage (due to light). Oxidative stress in the retina leads to increased amounts of lipofuscin - which is formed from oxidative by products and can trigger retinal damage and apoptosis. 
• LB has shown potential support for retinal diseases. While most studies have been in animal models, long term studies and human studies still need to be done. Retinal diseases which may benefit from LB include (3)
• Age-Related Macular Degeneration (AMD) - in early AMD LB has slowed progression and inhibited soft drusen formation.
• Diabetic Retinopathy (DR) - In animal studies, LB restored retinal thickness, reversed hyperglycemic oxidative stress, promoted reductions in retinal vascular changes seen in diabetic retinopathy. Reversed increased VEGF vascular growth factor - which increases vascularization in DR. Also enhanced protection of blood-retinal-brain barrier (which is disrupted by diabetes), causing macular edema. 
• Retinitis Pigmentosa - an inherited genetic disease of the retina. LB may improve visual processing by increasing antioxidant protection  of photoreceptors.
• LB significant increases antioxidation levels, while inhibiting lipid peroxidation (fatty acids are prevalent in photoreceptor membranes).
• LB is the richest source of natural Zeaxanthin. Contains very high bioavailable Zeaxanthin (demonstrated in animals and humans)

PROMOTES INTESTINE HEALTH / IMMUNE RESPONSE

• Strengthens the intestinal barrier, which is critical for maintaining a healthy functioning intestine.LB Promotes increased production of short chain fatty acids (which is anti-inflammatory)
• Promotes intestinal immunity (1)  Support general immune response through changes in gut microbiota  and increases in short chain fatty acids.(5)

PROTECTS LIVER 

• Attenuates liver cell damage from environmental contaminants (plastics), in addition to alcohol toxicity by increasing levels of Nrf2, a master regulator of cellular antioxidants in the cell. As a result,  Nrf2 triggers significant increases in cellular antioxidant activity and inhibiting apoptosis of the liver cells. Alcohol induced damage to the liver is a result of increased oxidative stress and destruction of the cells.(1,6,7)

VISION VITALITY  (Lycium Bararum)

REFERENCES:

(1) Ding Y, et al. Effects of long-term consumption of polysaccharides from the fruit of Lycium barbarum on host's health.  Food Res Int. 2021 Jan.

(2) Tang R, et al. Lycium barbarum polysaccharides extend the mean lifespan of Drosophila melanogaster.  Food Funct. 2019 Jul.

(3) Neelam K, et al. Fructus lycii: A Natural Dietary Supplement for Amelioration of Retinal Diseases. Nutrients. 2021 Jan.

(4) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice.

(5) Ding Y, et al. Modulating effects of polysaccharides from the fruits of Lycium barbarum on the immune response and gut microbiota in cyclophosphamide-treated mice. Food Funct. 2019 Jun.

(6) Liu R, et al. Protective effect of Lycium barbarum polysaccharide on di-(2-ethylhexyl) phthalate-induced toxicity in rat liver. Environ Sci Pollut Res Intl. 2021. Jan.

(7) Wang H, et al. Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against alcohol-induced oxidative damage involves Nrf2 signaling. Food Sci Nutr. 2020 Oct..

Two times Power of Anti-Aging Resveratrol - Ursolic Acid and Rosmarinic Acid

Resveratrol has long been known as an natural anti-aging gene activator. The target of this activation is SIRT1. Research now indicates that another extract  (ursolic acid) is even more powerful than resveratrol in the activation SIRT1. Furthermore, the extracts ursolic acid and rosmarinic acid promote anti-aging in other ways,, including preservation of the functioning of the hypothalamus (implicated as playing a significant role in the aging process), inhibiting fibrosis (amyloid and tau) and inhibiting NOX2 and NOX4.

URSOLIC ACID

• SIRT1 Activator - Ursolic acid is a powerful activator of anti-aging protein SIRT1. In fact, when compared to resveratol, ursolic acid is double the power of activating SIRT1 versus resveratol.(1)

• Hypothalamus Anti-Aging - Recent research indicates that the hypothalamus is an important determinant in longevity, Dysregulation of the hypothalamus during aging affects the neuroendocrine system, and contributes to the exhaustion of stem cells, and the loss of proteostasis.(2) Ursolic acid beneficially supports health of the hypothalamus by enhancing levels of anti-aging SIRT1, SIRT6, PGC-1β and α-Klotho.(3)

• Nrf2 Preservation - Nrf2 is the master protein activator of the endogenous antioxidant system in the body, and is related to increased longevity. Ursolic acid is a potent inhibitor of the degradation of Nrf2, which supports increased level of Nrf2. (4)

ROSMARINIC ACID

• Longevity Extender -  In experimental studies with c. elegans, rosmarinic acid significantly extended lifespan by increasing anti-aging gene expression of daf-16 and other proteins.(5) 

• NOX2 and NOX4 (NADPH oxidases) Inhibitor - NOX2 and NOX4 play critical roles in aging.
• NOX2 - involved in hypertension, atherosclerosis, cardiac hypertrophy, diabetes and aging. The inhibition of NOX-2 is proposed for maintaining cardiovascular homeostasis.(6)
• NOX4 - involved in cellular senescence. The inhibition of NOX-4 may support anti-aging in body, which is expressed in many organs in the body.(7)
• Both NOXs are viewed as potential therapeutic targets to block.
• Rosmarinic acid inhibits both NOX2 and NOX4.(7)

• Amyoid Aggregation Inhibitor  -  An important hallmark of aging, both in the brain (Alzheimers Disease) and throughout the body, is the formation of amyloid fibril aggregates.
• While resveratrol has been shown to be inactive in the inhibition of aggregate formation,  rosmarinic acid, is shown as a powerful inhibitor.(8)
• Tau Aggregation Inhibitor - Insoluble tau protein is another protein abnormality (in conjunction with amyloid) associated with Alzheimer's Disease in the brain. Aging and chronic stress may induce tau aggregation. In lab animals, rosmarinic acid was shown to reduce tau protein aggregation. (9)

• Glycation Inhibitor - Supports Elastic Arteries and Skin. Glycation is the damaging of protein structure, accelerating aging of all protein structures in the body. Includes loss of elasticity of skin and arterial function.
• Glycation results in stiffness of the skin (and old appearance) and arteries. All indicators of significant aging. Rosmarinic acid was shown to improve the parameters of skin and arterial elasticity in human test subjects.(10)

• Insulin Resistance - AMPK. Rosmarinic acid significantly reduced skeletal muscle insulin resistance in insulin resistant lab animals. Rosmarinic acid activated AMPK in the muscle, which resulted in increased mitochondrial biogenesis,(11)

HYPER LONGEVITY  (Ursolic Acid | Rosmarinic Acid)

REFERENCES:

(1) Bakhtian N, et al. Mounting evidence validates Ursolic Acid directly activates SIRT1: A powerful STAC which mimic endogenous activator of SIRT1. Arch Biochem Biophys. 2018 Jul

(2) Kim K, et al. Role of hypothalamus in aging and its underlying cellular mechanisms. Mech. Ageing Dev. 2018. May.

(3) Bahrami SA, et al Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level. Biomed Pharmacother, 2016 Aug

(4) Kamble SM, et al. In silico Evidence for Binding of Pentacyclic Triterpenoids to Keap1-Nrf2 Protein-Protein Binding Site. Comb Chem High Throughput Screen. 2017

(5) Wang F, et al. The Molecular Mechanism of Rosmarinic Acid Extending the Lifespan of Caenorhabditis elegans. Applied Mechanics and Materilals. 2011.

(6) Forte M, et al. The Pathophysiological Role of NOX2 in Hypertension and Organ Damage. High Blood Press. Cardiovasc Prev. 2016 Dec

(7) Revoltella S, et al. Identification of the NADPH Oxidase 4 Inhibiting Principle of Lycopus europaeus. Molecules. 2018 Mar.

(8) Ramazzotti M, et al, Mechanism for the inhibition of amyloid aggregation by small ligands.Biosci Rep. 2016 Sept.

(9) Shan Y, et al. Aging as a Precipitating Factor in Chronic Restraint Stress-Induced Tau Aggregation Pathology, and the Protective Effects of Rosmarinic Acid.  J Alzheimers Dis. 2016

(10) Yui S, et al. Beneficial Effects of Lemon Balm Leaf Extract on In Vitro Glycation of Proteins, Arterial Stiffness, and Skin Elasticity in Healthy Adults. J Nutr Sci Vitaminol (Tokyo) 2017

(11) Jayanthy G, et al, Rosmarinic Acid Mediates Mitochondrial Biogenesis in Insulin Resistant Skeletal Muscle Through Activation of AMPK. J Cell Biochem. 2017 Jul