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Prolongevity: New Evidence of Anti-Aging Effect of Resveratrol

For years, it has been known that resveratrol is one of the most effective anti-aging compounds studied. Beneficial effects on lifespan have been demonstrated across many research organisms, including worms and flies. In 2003, resveratrol was identified as a molecule which could activate SIRT1, mimicking the life extending benefits shown by calorie restriction. Furthermore, resveratrol also activates the anti-aging Nrf2 pathway, and AMPK which enhances NAD+ availability. (1) Cellular NAD+ levels are linked to longevity. 

In a new study, the silkworm was used to further illustrate the life extending effects of resveratrol via significant improvement of antioxidant activity.. Oxidation is a key factor is anti-aging and shortening of the lifespan.(2)

Resveratrol was shown to activate antioxidant function in the silkworm via increased activity of the GST enzyme, key in the antioxidant enzyme system.

RESVERATROL ACTIVATES the GST Antioxidant System via

• SIRT7 (activation) ---> activates FOXO --> activates GST (antioxidant) 

This research further validates the beneficial life extending benefits of resveratrol.

PURPLE LONGEVITY (Resveratrol : Pterostilbene)

REFERENCES:

(1) Li Z, et al. Aging and age‐related diseases: from mechanisms to therapeutic strategies. Biogerontology. 2021 Jan 

(2) Song J, et al.  Resveratrol elongates the lifespan and improves antioxidant activity in the silkworm Bombyx mori. J Pharm Anal. 2021 Jun

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..

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.

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.

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.