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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..

      CURCUMIN PXC® - The Proteostasis Curcumin® and Fisetin for Longevity

      PROTEOSTASIS. Defines the ability of the body to maintain the fidelity of  biogenesis of protein (non-defective proteins), folding. movement, and removal of old protein aggregates. Especially significant is the removal of old damaged protein aggregates, which are detrimental to the functioning of the cell. Clearing old cellular debris, through a process called autophagy, greatly enhances the youthful functioning of the cell. 

      CURCUMIN ENHANCES AUTOPHAGY. Lifespan and autophagy are strongly
       associated with one another.  Calorie restriction, resveratrol and curcumin are known to improve autophagy and increase lifespan. In fact, all life extension mechanisms depend upon the importance of autophagy for clearing cellular damage.(1,2)

      Aging affects molecular pathways that influence health and longevity. As a result, there is a reduction of cellular debris clearance (autophagy), decreased  the pool of stem cells, increase in inflammation and cellular senescence. 

       

      CURCUMIN has been shown to by positively regulate longevity by through important molecular pathways, including IIS, mTOR and FOXO. Curcumin is a powerful activator of the body's antioxidant defense system, as an Nrf2 activator. As an antioxidant, curcumin stabilizes and protects telomeres. Inflammation is also a powerful promoter of aging. Curcumin inhibits the powerful inflammation transcription factor NF-κB and is associated with reduced levels of inflammation.(3)  PROTEOSTASIS is impacted by all these aging pathways.(4) Therefore, curcumin supports longevity via aging signaling and proteostasis (autophagy).

      • NEURODEGENERATION AND AUTOPHAGY.

      Misfolded proteins in the brain are associated with poorly functioning autophagy. Autophagy removes aggregate protein accumulations which is responsible for neurodegeneration. Curcumin, research indicates, may help restore autophagy in the brain, to clear these misfolded proteins. (5) Oleuropein, a component of Olive Oil, in addition to curcumin, is implicated in mitophagy in the brain, removing old and dysfunction mitochondria. (6)

      • SIRT1 (SIRTUINS) ENHANCES PROTEOSTASIS

      SIRT1 is an enzyme which regulates cellular processes relative to longevity. SIRT1 INCREASES PROTEOSTASIS ,which is an important component of the longevity effect. Natural activators of SIRT1 include Curcumin, Fisetin, Quercetin and Resveratrol.(15)

      • ATRIAL FIBRILLATION: PROTEOSTASIS AUTOPHAGY & INFLAMMATION

      Cardiac remodeling through failure of autophagy, proteostasis and inflammation are believed to be a root cause of atrial fibrillation. Cardiomyocytes are replaced by non-functional proteins..(12. 13)  

      • PROTEOSTASIS DECLINE SIGNIFICANTLY IMPACTS AGING. (7)

      With age, cells become replicative scenescent - losing ability to produce new cells. Furthermore, scenescent cells are old cells. Old cells have been shown to lose proteostasis, which further limit the abilty of the cell to respond to external threats and maintain function. Curcumin and pterostilbene(11) helps inhibit cellular scenescence. Fisetin and quercetin are considered senolytics, which are capable of removing scenescent cells. (10)  Importantly, recent research also indicates that curcumin also removes scenescent cells.(14)

      CURCUMIN PXC® - Incorporates highly bioavailable curcumin  Furthermore, Curcumin PXC also includes powerful supplemental ingredients in support of proteostasis.

      • AUTOPHAGIX™ Complex - Rutin, Lonicera japonica (8), Oleuropein, Quercetin. 
      • ROSEMARY PROTEOSTASIS COMPLEX (9)
      • FISETIN (10)
      • TRANS-PTEROSTILBENE

       

      CURCUMIN PXC® - THE PROTEOSTASIS CURCUMIN® 

       

      REFERENCES:

      Rosmarinic Acid - Suppression amyloid beta / Tau, and/or α-synuclein

      The formation of insoluble fibers in the brain, including amyloid beta, Tau and α-synuclein are associated with dementia (especially correlated with aging). As such, targeted suppression and removal of these fibrils may be a strategic method of improving disease progression.

      Results of studies demonstrated that Spearmint extract and Rosmarnic Acid (a component of Spearmint) can suppress the formation of amyloid fibrils. Furthermore, Rosmarinic Acid may breakdown already formed amyloid beta, Tau and α-synuclein fibrils.(1) Myricetin, another phenolic compound, also exhibits suppression of α-synuclein fibrils.(2)

      In the brain, dementia Lewy Bodies involve primarily α-synuclein fibrils, while Alzheimer's Disease involve primarily amyloid beta fibrils.

       

      HYPER LONGEVITY®  (contains ROSMARINIC ACID / MYRICETIN)

      CURCUMIN PXC® (contains ROSMARINIC ACID)

      NEUROTREX® (contains ROSMARINIC ACID / MYRICETIN)

       

      REFERENCES:

      1. Ojawa K,  et al. Spearmint Extract Containing Rosmarinic Acid Suppresses Amyloid Fibril Formation of Proteins Associated with Dementia. Nutrients. 2020 Nov 13.

      2. Takahashi R, et al. Phenolic compounds prevent the oligomerization of α-synuclein and reduce synaptic toxicity. J Neurochem. 2015 Sep.

      Suppressing Peripheral Nerve Degeneration With Aging - Apigenin

      Aging has a direct effect on the nervous system, In the central nervous system, aging affects the brain with dementia and Alzheimer's and other brain diseases. Similarly,  the peripheral nervous system, which consists of nerves extending from the brain and central nervous system, undergoes degeneration.(1)  As such, in the elderly there is a decrease in sensory and motor nerve conduction and amplitude.(2) Extremity pain, tingling, numbness, loss of balance. swallowing problems, are all related to peripheral nerve degeneration In diabetics, there is increased rate of  peripheral nerve degeneration.

      AGING: LOSS OF NERVE FIBER - DECLINE IN NERVE CONDUCTION VELOCITY.

      Structural changes to nerves occur with age, including decreases in amount of nerve fiber. While both myelinated  an unmyelinated  fibers are both affected, unmyelinated are most sensitive. Furthermore, loss of nerve conduction velocity is contributed by decrease axon diameter and reduced myelination of the nerve.

      APIGENIN DELAYS THE DEGENERATION OF PERIPHERAL NERVES

      According to recent research, apigenin has been shown to protect the degeneration of peripheral nerves with age  Much of this protection is due to the reversal of chronic oxidative stress in the peripheral nerves.(3) Major areas of protection by Apigenin:

      • AXONAL DEGENERATION - The nerve fiber which transmits electrical impulses away from the nerve cell body. Apigenin protects the axon against degeneration
      • MYELIN FRAGMENTATION - Myelin surrounds the axon, and functions as an insulation to the axon as well as increases speed of electrical transmission, Myelin fragmentation is the degenerative breakdown of the myelin sheath. Apigenin inhibits degeneration of myelin.
      • SCHWANN CELL PROLIFERATION. Is a myelinating glial cell, which  support the peripheral nervous system. Specifically, Schwann cells produce the myelin around the axon. Aged Schwann Cells impair the plasticity and the ability of the peripheral nerve system to regenerate. (4) Apigenin increases the number of Schwann cells.

       

       YELLOW LONGEVITY  (APIGENIN) 

       

      REFERENCES:

      (1) Painter M. Regeneration in the aging peripheral nervous system. Harvard University. 2014

      (2) Bouche P. Neuropathy of the elderly. Rev Neurol (Paris). 2020 Sept 23.

      (3)  Muwoong Kim. et al.  The Natural Plant Flavonoid Apigenin Is a Strong Antioxidant That Effectively Delays Peripheral Neurodegenerative Processes. Anal Sci Int. 2019 Sept.

      (4) Painter M, et al. Diminished Schwann cell repair responses underlie age-associated impaired axonal regeneration. Neuron. 2014 Jul.

      Meso Zeaxanthin - Macular Degeneration Lipofuscin & The Aging Retina

      RETINAL AGING. The component of the retina which is essential for maintaining visual function and photoreceptor survival  is the Retinal Pigment Epithelium (RPE).(1)  The RPE provides the homeostasis of the retina, including phagocytosis, a process by which the shedding of the outer segments of photoreceptors is removed and properly disposed as waste products. It is critical that phagocytosis provide daily removal of the shedded segments to maintain vision.  Phagocytosis denote a highly active lysosomal activity in the RPE of the retina. Aging of retinal results in a degression of lysosomal activity and accumulation of waste material (Lipofuscin). (2) Furthermore, age related photooxidation of the cellular membrane of the retina further damages the RPE and retinal function.  

      LIPOFUSCIN AND MACULAR DEGENERATION. Lipofuscin is generated through oxidative stress and a result of waste products. When the retina loses phagocytosis, there is photoreceptor degeneration.(1) Diminished phagocytosis results in increased lipofuscin accumulated in the RPE, which in turn negatively affects the RPE and photoreceptors. Lipofuscin levels also increase through oxidative stress in the retina. Accumulation of lipofuscin is an indicator of RPE atrophy and macular degeneration. As powerful antioxidants, lutein and zeaxanthin can reduce formation of lipofuscin. Zeaxanthin in particular can further help by supporting the phagocytosis removal of lipofuscin.(3,4)

      The RPE contains the pigments melanin (in melanosomes) and lipofuscin. Melanin is an antioxidant pigment, whereas lipofucsin is the byproduct of waste material from photoreceptor removal and oxidative stress, which increases with dysfunction of phagocytosis. The accumulation of lipofuscin  reduces the protection of melanin and increases oxidative stress of the RPE.(2)  

      While melanin is a powerful protector of the retina, aging affects the ability of melanin to protect the eye. Older melanosomes exposed to blue light, significantly inhibited phagocytosis - which accelerated degeneration of photoreceptors.. Therefore, the phototoxicity of melansomes increase with age. However, the antioxidant zeaxanthin has been shown to reduce the phototoxicity potential.(3)

      ZEAXANTHIN HELPS PROTECTS AGAINST RETINAL DEGENERATION

      (1) By reducing Phototoxicity / Photooxidation damage of retinal cellular membranes associated with aging.

      (2) By supporting Phagocytosis.and the Maintenance of the RPE. 

      Meso zeaxanthin is the most powerful version of zeaxanthin, and is found in the central macula.

       

       VISION VITALITY  (MESO ZEAXANTHIN)

       

      REFERENCES:

      (1) Valiente-Soriano F, et al. Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium.Sci Rep. 2020.

      (2) Bonilha V.. Age and disease-related structural changes in the retinal pigment epithelium. Clin. Ophthalmol. 2008 Jun

      (3) Olchawa M, et al. The effect of aging and antioxidants on photoreactivity and phototoxicity of human melanosomes; an in vitro study. Pigment Cell Melanoma Res, 2020 Jul 23.

      (4) Olchawa M, et al. Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells. Free Radic Biol Med. 2015 Dec.

      Glycation - Implications for Proteostasis (Autophagy) and Extracellular Matrix Aging

      Aging is a complex consequence of many factors. Cellular age post-translational non-enzymatic protein modifications is considered as critical in this model. Glycation is damaging of protein structures ,via non-enzymatic binding of glucose to protein. Glycation results in damaged proteins which affects functioning inside the cell and outside the cell. Advanced glycation end products (AGEs) are subsequently formed, and trigger oxidative stress and inflammation. Furthermore, inflammation, age-related oxidative stress, as well as decreased levels of NAD+ in the cell all affect proteostasis, a critical factor in longevity.(1,2) An important function of proteostasis is autophagic clearance of damaged and toxic proteins, such as amyloid.

      GLYCATION - INTRACELLULAR AGING

      With age, there is a buildup of advanced glycation end products (AGEs) in the cell. AGEs  create additional oxidative stress and inflammation in the cell. AGEs also reduce cellular proteostasis, which further reduces the cells ability to eliminate AGE complexes through autophagy. The accumulation of AGEs in cardiac and vascular cells, lead to inflammation and fibrosis, causing atherosclerosis and cardiac diseases. (3)

      GLYCATION - EXTRACELLULAR  AGING

      In particular, modifications such as cross-linking of long-lived molecules with slow turnover. In the extracellular matrix (ECM), the cross-linking of molecules such as collagen and elastin, create loss of cellular homeostasis, especially proteostasis. The cross-linking of these long-lived molecules occur through processes such as glycation. Creates an abnormal stiffness and hardening from which cannot be recovered. Stiffness of the ECM contributes to hypertension, rigidity of arteries, atherosclerosis and cancer.(4)

      Perhaps most important, these alterations of ECM reduce viability of the cell, reducing longevity.  Due to the diminishing amount of functional elastin, it has been suggested that the maximum limit for elastin dependent cardiovascular and respiratory systems is 100-120 years.(5)

      ECM aging is also linked to stem-cell aging, and exhaustion of the stem cell supply. (4)  Interestingly, older mouse cells transplanted into younger mice, may outlive the maximum lifespan of an organism by three-fold! This exemplifies the importance of the extracellular environment and how stiff ECM affects cellular lifespan.

      Further linkage between ECM stiffness and cellular senescence. Which may also be associated with increased fibrosis. FIBROSIS. Is another key aging indicator. Mitochondrial dysfunction also increases in frequency in a aged (stiff) ECM. Skin aging is accelerated by ECM stiffness, which causes increase in breakdown of skin layers.

      ATRIAL FIBRILLATION. Advanced glycation endproducts are involved in the pathogenesis of Atrial fibrillation. (6) Suggested modes of treatment include lowering AGE levels and increasing levels of antioxidants.(9)

       

      BOTANICAL EXTRACTS FOR AGING INHIBITION

      • APIGENIN / ANTI-GLYCATION

      Apigenin prevents the formation of AGEs by trapping methylglyoxal (MGO), which is a precursor molecule. Through inhibiting MGO, AGEs will not be formed, thereby reducing oxidative stress and inflammation. In turn, this allows for increased proteostasis in the cell.(6)  

        • APIGENIN / CD38 (NAD)
          An important anti-aging molecule NAD signicantly decrease in aging cells. An enzyme CD38, an enzyme found inflammatory cells,  is responsible for decreasing levels of cellular NAD, In fact, older humans were found to have almost three times the levels of CD38 versus younger counterparts.  Apigenin inhibits CD38, thereby increasing levels of NAD+.

          Sufficient levels of cellular NAD+ are required for anti-aging cellular        functions, including proteostasis. (7,8) The principal regular for cellular NAD+ in cells is CD38.

          • BERBERINE  (ANTI-GLYCATION / ANT-FIBRIL / ANTI-AMYLOID)

          In animal research experiments, berberine reduced glycation levels. (10) In the brain of Alzheimers Disease mice, berberine invoked autophagic clearance of amyloid beta deposits.(11)  Also has been shown to reduce the formation of amyloid beta oligomer formation, this is the prior step  before amyloid beta fibril formation. (12) When combined with curcumin, there is a synergistic reduction in amyloid beta production.(13)

          • ROSMARINIC ACID (ANTI-GLYCATION / ANTI-AGGREGATION)

          Research indicates that rosmarinic acid both inhibits glycation and prevents protein aggregation. Both are correlated to aging pathologies.(14).

          • CURCUMIN  (ANTI-GLYCATION / AUTOPHAGY / ELASTIN MATRIX)
          Curcumin has been shown to markedly lower AGE levels in lab animals.(15) Specific studies animal models showed significant increases in antioxidant levels and an increase in the AGE detoxification system.
          AMYLOID INHIBITION - Inhibits production of amyloid and increases autophagic removal of amyloid. Acts synergistically with berberine.(13)
          ELASTIN MATRIX. Curcumin enhances production of elastin fbers (Elastiin and fibrillin-1) which are components of the extracellular matrix (along with collagen). Studies indicate that curcumin supports arterial and lung elasticity.(16).
          • FISETIN (Traps MGO which prevents AGE formation)(17)
          • PTEROSTILBENE (Traps MGO which prevents AGE formation )(18)
          • RUTIN (inhibits generation of AGEs)(19)

           

           YELLOW LONGEVITY®  (APIGENIN | BERBERINE | FISETIN | CURCUMIN)

           CURCUMIN PXC®  (CURCUMIN | ROSMARINIC | FISETIN |PTEROSTILBENE)

           

          REFERENCES:

          (1) Baldensperger T, et al. Comprehensive Analysis of Posttranslational Protein Modifications in Aging of Subcellular Compartments. Sci Rep. 2020 May.

          (2) Rudzinnska M, et al. Cellular Aging Characteristics and Their Association With Age-Related Disorders. Antioxidants (Basel). 2020 Jan.

          (3) Neviere R, et al. Implication of Advanced Glycation End Products (Ages) and Their Receptor (Rage) on Myocardial Contractile and Mitochondrial Functions. Glycoconj J. 2016 Aug.

          (4) Fedintsev, A. et al. Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging. Ageing Research Reviews. Volume 62. September 2020.

          (5) Robert L, et al. Rapid Increase in Human Life Expectancy: Will It Soon Be Limited by the Aging of Elastin? Biogerontology. 2008. Apr.

          (6) Zhou, Q. et al. Apigenin and Its Methylglyoxal-Adduct Inhibit Advanced Glycation End Products-Induced Oxidative Stress and Inflammation in Endothelial Cells. Biochem Pharmacol. 2019 Aug.

          (7) Griffiths H, et al. Nicotinamide Adenine Dinucleotide (NAD+): Essential Redox Metabolite, Co-Substrate and an Anti-Cancer and Anti-Ageing Therapeutic Target

          (8) Ogura Y, et al. CD38 Inhibition by Apigenin Ameliorates Mitochondrial Oxidative Stress Through Restoration of the Intracellular NAD +/NADH Ratio and Sirt3 Activity in Renal Tubular Cells in Diabetic Rats. Aging (Albany NY). 2020 Jun

          (9) Prasad K. AGE-RAGE Stress in the Pathophysiology of Atrial Fibrillation and Its Treatment. Int J Angiol. 2020 Jun.

          (10) Zych M, et al. Effect of Berberine on Glycation, Aldose Reductase Activity, and Oxidative Stress in the Lenses of Streptozotocin-Induced Diabetic Rats In Vivo-A Preliminary Study. Int J Mol Sci. 2020 Jun.

          (11) Huang M, et al. Berberine Improves Cognitive Impairment by Promoting Autophagic Clearance and Inhibiting Production of β-amyloid in APP/tau/PS1 Mouse Model of Alzheimer's Disease. Exp Gerontol, 2017 May.

          (12) Fawver J, et al. Probing and Trapping a Sensitive Conformation: Amyloid-β Fibrils, Oligomers, and Dimers. J Alzheimers Dis. 2012.

          (13) Lin L, et al.  Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model. Neurochem Res. 2020 May.

          (14) Shamsi A, et al. Rosmarinic Acid Restrains Protein Glycation and Aggregation in Human Serum Albumin: Multi Spectroscopic and Microscopic Insight - Possible Therapeutics Targeting Diseases. Int J Biol Macromol. 2020 Jun.

          (15) Lima T, et al. Curcumin, Alone or in Combination With Aminoguanidine, Increases Antioxidant Defenses and Glycation Product Detoxification in Streptozotocin-Diabetic Rats: A Therapeutic Strategy to Mitigate Glycoxidative Stress. Oxid Med Cell Longev. 2020 May.

          (16) Lee S, et al. Curcumin Enhances the Production of Major Structural Components of Elastic Fibers, Elastin, and fibrillin-1, in Normal Human Fibroblast Cells. Biosci Biotechnol Biochem. 2015.

          (17) Maher P, et al. Fisetin Lowers Methylglyoxal Dependent Protein Glycation and Limits the Complications of Diabetes. PLoS One. 2011.

          (18) Lv, L, et al. Stilbene Glucoside From Polygonum Multiflorum Thunb.: A Novel Natural Inhibitor of Advanced Glycation End Product Formation by Trapping of Methylglyoxal. J Agric Food Chem. 2010 Feb.

          (19) Liang W, et al. Protective Effects of Rutin on Liver Injury in Type 2 Diabetic db/db Mice. Biomed Pharmacother. 2018 Nov.

           

          Natural Yellows - For Obesity and Non-Alcoholic Liver Disease

          Excess body weight is associated with many health concerns, and is rapidly  becoming the number one health problem worldwide. among the health risks are diabetes, cardiovascular disease, cancer and premature death. (1)  Individuals of the obese classification are especially subject to deleterious health implications. Obesity results in:

          • Visceral Fat. Excessive adipose tissue, especially dangerous visceral fat surrounding internal organs, and
          • Non-alcoholic fatty liver disease (NAFLD) is the most ubiquitous cause of liver disorder worldwide and is attributed to obesity and diabetes. NAFLD affects approximately 25% of the global population.(22). Insulin resistance is a major contributor to NAFLD. Ultimately, NAFLD may lead to liver cirrhosis and liver failure.

           

          Visceral Fat - Obesity results in increases of visceral fat. Visceral fat (also known as belly fat) is the fat that accumulates around organs in the abdominal cavity and is linked to serious diseases, including type 2 diabetes. metabolic syndrome and those affecting organ functioning. Significant levels of inflammatory proteins are generated by visceral fat. In fact, inflammation of the liver which precedes HDLF, is mediated by visceral fat inflammatory proteins.(2)

          • Heart visceral fat - Accumulation of fat surrounding the heart may have profound effects on the myocardium and functioning of the heart. In obese lab animals, the heart visceral fat (white fat) increased inflammation of the heart, including hypertrophy of the cardiomyocytes and fibrosis. Further, these changes to the heart are significantly related to increased rates of heart failure.(3) Such changes were not seen in lean animals which had a significant amount of brown fat adjacent to the heart muscle.
          • Kidney visceral fat - Visceral fat deposits around the kidney are associated with both chronic kidney disease as well as cardiovascular disease.(4)
          • Pancreatic Visceral Fat - Increased levels of pancreatic fat coincide with pancreatic cancer and pre-cancer lesions.(5)

            Nonalcoholic fatty liver disease (NAFLD) - Obesity is a significant risk factor in the development of NAFLD.  Most noteworthy, is the excessive buildup of triglycerides in the liver which causes metabolic disturbances throughout the body. As a result, fatty acid metabolism becomes impaired, which may lead to fatty acid intermediates which causes insulin resistance and cardiovascular disease. 

            Adipose Tissue and Aging - White adipose tissue, associated with obesity,  is the most affected tissue in aging. As the adipose tissue ages, there is a significant increase in oxidative stress and the generation of  inflammatory proteins resulting in  chronic low grade inflammation. In turn, this further damages tissue and accelerates aging. (6) 

            • Telomere Shortening - Telomere shortening is a marker of aging. (7) Appears to be associated with obesity and increased insulin resistance.
            • Insulin Resistance - Insulin resistance prevents blood sugar from being removed from the blood. The result is hyperglycemia which damages structures in the body. Eventually this become diabetes.
            • Diminishes Immune Response - Increased inflammation from adipose tissue contributes to loss of innate immunity response during aging.(8)
            • Impairs Stem Cell Regenerative Ability - Adipose tissue stem cells are impacted by adipose tissue inflammation. The result is the senescence of the stem cells and loss of tissue repair and regeneration.(9).
            • Loss of Healthy Fat Cell (Stromal Cells) Renewal - Healthy adipose tissue requires renewal of adipose stromal cells. The stromal cells ensure the production of new healthy adipose cells. Obesity contributes to the loss of the stromal cells.(10)

            INGREDIENTS:

            • Berberine - Inhibits the inflammation of the liver associated NAFLD. Inflammation is a key event in the progression of NAFLD. (11) Also enhances brown adipose fat activity, which promotes thermogenesis, which dissipates harmful white adipose tissue,(12) Furthermore, berberine inhibits the proliferation of white fat adipocytes, thereby suppressing the formation of fat associated with obesity.(13) Berberine also reduces insulin resistance which improves glucose tolerance and NAFLD.(14).
            • Apigenin - Reduces abdominal visceral obesity and weight. Abdominal visceral fat promotes metabolic syndrome including inhibition of adipocytes  (fat cells). Does not affect subcutaneous fat, which lies just under the skin.(15) Apigenin also improves NAFLD and Insulin resistance.(16) 
            • Saffron - Improves insulin sensitivity,(16) Possesses a protective effect against NAFLD and fatty liver induced damage.(17)
            • Curcumin - Reduces insulin resistance by enhancing GLUT4 gene expression (the receptor for Glucose transport into the cell).(18)
            • Fisetin - Offers protection to suppress NAFLD initiation and progression.(19)
            • Rosmarinic Acid - Ameliorates liver damage by NAFLD, by increasing antioxidant enzymes and activating AMPK. inhibiting hepatic fibosis and inflammation of the liver.(20) Rosmarinic acid also acts as an anti-obesity agent by inhibiting adipogenesis (the formation of fat tissue), and increasing lipolysis (the breakdown of fat), Also reduced adipocyte associated inflammation.(21)
            • Pterostilbene -  Enhances brown adipose tissue activation. Increases thermogenesis and promotes browning of white adipose tissue,(23) Offers protective effect on liver steatosis.(24)
            • Ursolic Acid - Targets insulin resistance and mitigating the effects of liver fibrosis. (25,26) Obesity disrupts insulin signaling, thereby promoting insulin resistance. Furthermore, visceral fat in obesity sets off cascading generation of proinflammatory cytokines. Ursolic acid may improve these conditions. 

             

            YELLOW LONGEVITY® (Berberine | Apigenin | Saffron)

            VASCULAR VX™

             CURCUMIN PXC(Curcumin | Fisetin | Pterostilbene) 

             HYPER LONGEVITY™ (Ursolic Acid | Rosmarinic Acid)

             

            REFERENCES:

            (1)  Unamuno Xm et al. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest. 2018 Sep

            (2)  Casagrande BP, et al. Hepatic inflammation precedes steatosis and is mediated by visceral fat accumulation.  J Endocrinol. 2020 Mar 1

            (3) Conceição G, et al. Fat Quality Matters: Distinct Proteomic Signatures Between Lean and Obese Cardiac Visceral Adipose Tissue Underlie its Differential Myocardial Impact. Cell Physiol Biochem. 2020 Apr 23

            (4) Huang N, et al. Novel insight into perirenal adipose tissue: A neglected adipose depot linking cardiovascular and chronic kidney disease. World J Diabetes, 2020 Apr 15

            (5) Sreedhar UL, et al. A Systematic Review of Intra-pancreatic Fat Deposition and Pancreatic Carcinogenesis. J Gastrointest Surg. 2019 Nov 20

            (6) Yu Q, et al. Sample multiplexing for targeted pathway proteomics in aging mice. Proc Natl Acad Sci USA. 2020 Apr 24

            (7) Mangge H, et al. Telomere shortening associates with elevated insulin and nuchal fat accumulation. Sci Rep. 2020 Apr 22

            (8) Goldberg EL, et al. How Inflammation Blunts Innate Immunity in Aging. Interdiscip Top Gerontol Geiatr.  2020

            (9) Conley SM, et al. Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells. Front Cell Dev Biol. 2020 Mar 26

            (10) Eckel-Mahan K, et al. Adipose Stromal Cell Expansion and Exhaustion: Mechanisms and Consequences. Cells 2020 Apr 2

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