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Naked Mole Rats - Clues to their Exceptional Longevity

Naked Mole Rats (NMR),  native to parts of East Africa, are extremely long lived rodents, living up to 8x's longer than comparably sized mice. This is equivalent to a humans living to be 800 years! Better yet, the NMR maintain their vitality and health to almost the end of their lives, including brains which are resistant to degeneration. So, what is behind such extreme longevity?

The key is enhanced cellular protein homeostasis. (1-3) Key regulators of the aging process is the ability to maintain cellular quality including the removal of defective, damaged and toxic proteins. In the cell, proteasomes, the cellular machinery which removes damaged protein in conjunction with lysosomal  autophagy are involved in the removal of damaged protein and cellular components. NMR maintain a very high level of protein homeostasis by enhanced activity of proteasomes and maintaining high active levels of autophagy.

Increased proteasome and autophagy activity extends lifespans in animal experiments. However, dysfunction of protein homeostasis increases with age, and leads to cellular accumulation of damaged protein, and the onset of disease and aging. In Alzheimer's Disease, for example, damaged proteins (amyloid and tau proteins) begin to aggregate, and eventually kill the surrounding neurons. Normal protein homeostasis is disrupted in Alzheimer's Disease, and most notably impairment of autophagy.(4)  

PROTEIN HOMEOSTASIS is essential for extreme longevity. The two primary molecular mechanisms for maintaining health cell quality control and protein are: Proteasomes and Autophagy. "Aging is considered to be the loss of physiological integrity accompanied by a cumulative dysfunction in securing cellular homeostasis, resulting in the accumulation of damage and a progressive decline of cellular function over time." (7) 

  • Proteasomes-  In the cell it is the function of structures called proteasomes, to identify and remove damaged proteins.  Damaged proteins are tagged and then subsequently degraded by the proteasomes. Aging creates an imbalance in protein homeostasis, whereby proteasomes become dysfunctional.
  • Autophagy - Is the quality control in the cell which removes and recycles damaged and non-functional components (organelles and protein) through lysosomal degradation. Animals studies clearly demonstrate that in autophagy deficient mutants, lifespan is significantly reduced. Autophagy works in conjunction with protesomes  to maintain cellular health and extend longevity.
  • Heat Shock Proteins (HSP) - HSP are involved as sentries and chaperons, which monitor the cell for damaged proteins and ensure that they are rapidly degraded and recycled. HSPs work in conjunction with the proteasome system to prevent the accumulation of misfolded and toxic proteins in the cell. HSP identifies damaged misfolded proteins for proteasome degradation. HSP increase longevity, however levels decrease with aging.(10,11)

    FOXO Nrf2 (transcription factors) AND PROTEIN HOMEOSTASIS:

    • FOXO transcription factors are key regulators of cellular quality control including protein homeostasis
    • FOXO is required for the activation of proteasome and autophagy. (5,12)
    • Nrf2 is key for maximal expression of proteasomes for cellular protein homeostasis.(13)
    NATURAL SUPPORT OF PROTEIN HOMEOSTASIS:
    • Sulforaphane increases both proteasome activity and autophagy.(10) Increased activation of Nrf2 by sulforaphane is an important pathway by which proteasomal activity is increased.(9,11) Also sulforaphane upregulates heat shock proteins (HSP), which further elevates the protein degradation functioning of the proteasomes.(14)
    • Curcumin supports protein homeostasis through enhanced autophagy and HSP (Heat stress proteins)(16, 17)) and Nrf2 activation (13).
    • Resveratrol and Calorie Restriction also increase autophagy and extend lifespan.(15)

       

      XGEVITY (Glucoraphanin / Sulforaphane)

      AIR VITALITY (Glucoraphanin / Sulforaphane)

      CURCUMIN XTRA-MAX

      PURPLE LONGEVITY (Resveratrol)

       

      REFERENCES:

      (1) Triplett JC, et al. Age-related changes in the proteostasis network in the brain of the nakedmole-rat. Implications promoting healthy longevity. BiochimBiophys Acta. 2015 Oct.

      (2) Triplett JC, et al. Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat. J Neurochem. 2015 Aug.

      (3) Pride H, et al. Long-lived species have improved proteostasis compared to phylogenetically-related shorter lived species. Biochem Biophys Res. Commun. 2015 Feb.

      (4) Chondrogianni N, et al. 20S proteasome activation promotes life span extension and resistance to proteotoxicity in Caenorhabditis elegans. FASEB J. 2015 Feb

      (5) Chondrogianni N, et al. Enhanced proteasome degradation extends Caenorhabditis elegans lifespan and alleviates aggregation-related pathologies. Free Radic Biol Med. 2014 Oct.

      (6) Salminen A, et al. Impaired autophagy and APP processing in Alzheimer's disease: The potential role of Beclin 1 interactome. Prog. Neurobiol. 2013 Jul-Aug;

      (7) Grimmel M, et al. WIPI-Mediated Autophagy and Longevity. Cells. 2015 May.

      (8) Liu Y, et al. Sulforaphane enhances proteasomal and autophagic activities in mice and is a potential therapeutic reagent for Huntington's disease. J Neurochem 2014 May

      (9) Chapple SJ, et al. Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging. Int J Biochem Cell Biol. 2012 Aug

      (10) Murshid A, et al. Stress proteins in aging and life span. Int J Hyperthermia. 2013 Aug.

      (11) Calderwood SK, et al. The shock of aging: molecular chaperones and the heat shock response in longevity and aging--a mini-review. Gerontology. 2009.

      (12) Webb AE, et al. FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci. 2014 Apr.

      (13) Pickering AM, et al. Nrf2-dependent induction of proteasome and Pa28αβ regulator are required for adaptation to oxidative stress. J Biol Chem. 2012 Mar.

      (14) Gan N, et al. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27. J Biol Chem. 2010 Nov.

      (15) Testa G, et al. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr. Pharm Des. 2014

      (16) Petrovski G, et al. Does autophagy take a front seat in lifespan extension? J Cell Mol Med. 2010 Nov

      (17) Alavez S, et al. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature. 2011 Apr.

      Atrial Fibrillation : Effects of Aging and Endurance Sports

      ATRIAL FIBRILLATION (AF) is the most common arrhythmia of the heart and is caused when the atrial contraction becomes out of sync with the ventricle due to dysfunctional electrical signaling. The result is the ineffective movement of blood through the body. Atrial fibrillation may result in a fast fluttering heartbeat, which is a common characteristic. Because the blood is not being pumped through the body properly, atrial fibrillation increases risk of heart failure and the pooling of blood in the heart, which increases chances of blood clot formation. Blood clots which travel to the brain may cause a stroke.

      Risk of atrial fibrillation increases with age which coincides with increased oxidative stress, where excessive free radicals exceed the body’s ability to protect against them. Oxidative stress activates inflammatory pathways and chronic inflammation. Mitochondrial production of free radicals is a major source of oxidative stress in the atrial cells. Onset of atrial fibrillation includes changes to the atrial myocardium which includes inflammation and fibrosis which effects changes to the electrical properties and loss of synchronization. Therefore, research suggests two important factors may play a role in the alteration of the atrial cells and electrical impulse: Oxidative stress and inflammation.


      AGING AND ENDURANCE EXERCISE


      • AGING: A prominent risk factor for atrial fibrillation is aging. Aging is correlated with increased levels of systemic oxidative stress and inflammation.
      • ENDURANCE EXERCISE: AF has an increased occurrence in athletes, in particular those involved in endurance exercise (e.g. long distance running). The frequency of AF in endurance athletes is most notable in veteran endurance athletes (from ages 45 and higher). (1,2)
      • During endurance exercise, versus moderate exercise, repeated strenuous overloads of the atria result in microtears and consequently inflammation and fibrosis.(2)


      NATURAL SUPPORT:

      Inhibition of oxidative stress and inflammation of the artrial myocardial tissue, which reduces potential for fibrosis in the atria, are key in reducing the risk for atrial fibrillation. Beneficial steps:


      • INCREASING NRF2 – Nrf2 is a transcription factor which regulates the expression of proteins involved with cellular protection. Deficiency of Nrf2 reduces levels of protective proteins and facilitates the pathogenesis of structural changes to the atrial tissue, including fibrosis.(3-6) The condition of AF continues the cycle of oxidative stress, further altering the atrial tissue.
      • INHIBITION OF INFLAMMATION. TNF-alpha and NK-BKappa are signaling proteins which are central to the inflammatory pathway activation. TNF-alpha plays an important role in the pathogenesis of atrial structural changes and atrial fibrillation.(6)
      • ROLE OF NRF2 ACTIVATORS such as sulforaphane (and precursor glucoraphanin), supports the reduction of the tissue oxidative state while concurrently reducing the activation of the formation of fibrotic atrial tissue.(3-6) The Nrf2 activators, as powerful cell protectors, also support inflammation reduction and decrease expression of proinflammatory TNF-Alpha and NF-KappaB,
      • RESVERATROL may also have direct effects on cardiac function and the pathways that affect the structural changes to the atria. Recent research indicates that resveratrol may inhibit changes to the atria with decreased atrial fibrosis formation.(7-8)

      XGEVITY    (Glucoraphanin / Sulforaphane plus other Nrf2 activators)

      PURPLE LONGEVITY    (Resveratrol plus Nrf2 activators)

       


      REFERENCES:

      (1) Laszio R, et al. Atrial fibrillation and physical activity: An overview. Herz. 2015 Sept.
      (2) Redpath CJ, et al. Atrial fibrillation and the athletic heart. Curr Opin Cardiol. 2015 Jan.
      (3) Hecker L, et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med. 2014 Apr
      (4) Wolke C, et al. Redox control of cardiac remodeling in atrial fibrillation. Biochim Biophys Acta. 2015 Aug;
      (5) Yeh YH, et al. Rosuvastatin suppresses atrial tachycardia-induced cellular remodeling via Akt/Nrf2/heme oxygenase-1 pathway. J Mol Cell Cardiol. 2015 May.
      (6) Ren M, et al. Role of tumor necrosis factor alpha in the pathogenesis of atrial fibrillation: A novel potential therapeutic target? Ann Med. 2015 Jun
      (7) Baczkó I, et al. Resveratrol and derivatives for the treatment of atrial fibrillation. Ann N Y Acad Sci. 2015 Aug
      (8) Chong E, et al. Resveratrol, a red wine antioxidant, reduces atrial fibrillation susceptibility in the failing heart by PI3K/AKT/eNOS signaling pathway activation. Heart Rhythm. 2015 May

      Apigenin & Luteolin - Anti-Aging NAD+ Inflammatory Regulators & Brain Homeostasis

      POWERFUL YELLOWS AND AGING. Apigenin and Luteolin. Many changes occur during the aging process, with the most profound being inflammation. Inflammation contradicts good health and becomes increasingly unregulated with age. Since inflammation is key in accelerating aging, it is important to modulate these effects, especially in the brain.

      The gradual destruction of neurons by chronic inflammation (neuroinflammation) leads to brain deterioration and pathologies. In the arteries, inflammation facilitates the initiation and rapid onset of arteriosclerosis. It also is responsible for creating immune system dysfunction and autoimmune disease. Another affliction of the aging process is cancer, which is tightly associated with inflammation and cellular dysregulation. Apigenin and luteolin have both shown promise in supporting health aging including ensuring a healthy inflammatory response.  

          Longevity NAD+.

          • Apigenin increases levels of NAD+, which is a limiting factor in the ability of SIRT1 to enable numerous longevity effects. Apigenin works to increase NAD+ is via inhibition of CD38, which breaks down NAD+.(1)
          • High levels of NAD+ (via SIRT1 activation)  results in inhibition of obesity in high fat diets, metabolic syndrome and  glucose intolerance.
          • Degenerative brain disease associated with aging have high levels of CD38 and consequently low levels of NAD+. Therefore, apigenin may play an important role in increasing NAD+ in the brain and may mitigate brain degeneration. Biogerontology. 2014 Apr (2)

            Nrf2 Activation.

            • Nrf2 is a transcription factor is the trigger the cellular response to protect against damaging oxidative stress, including injury and inflammation as well as cellular homeostasis. Researchers suggest that Nrf2 may have a major impact on the health and lifespan.(3)
            • Apigenin and luteolin are both Nrf2 activators.(4)

              Inflammation

              • Inflammatory diseases are prevalent in the aging population, as inflammation becomes a chronic condition with age. Moreover, inflammation is the  primary factor for the development of chronic ailments and skyrocketing health care costs with age.
              • Chronic inflammation destroys the body (including the brain). This is not the normal immune system response, but  a chronic overstimulation, which continuously exposes the body to destructive and age accelerating inflammation. Such inflammation is normally low grade and the effects may take years to be evident.
              •  Apigenin and luteolin have significant anti-inflammation properties, and may significantly reduce chronic inflammation.

                Cardiovascular Artery Inflammation

                • Oxidized LDL in arteries causes macrophage inflammation in the arteries which promotes arteriosclerosis. It is the survival and continued activation of the macrophages in the arteries which keep the arteries inflamed. Apigenin can induce autophagy of macrophages, thereby reducing inflammation and inhibit the progression of atherosclerosis.(5-6) 

                  Brain Degeneration / Neuroinflammation

                  • Inflammation. All Neurodegenerative diseases have chronic immune activation, in particular microglia inflammation, as a common feature. Over activation of microglia in the brain, creating a low grade chronic source of inflammation, slowly degenerates the neurons and other cognitive structures.
                  • Importantly, in the brain, apigenin and luteolin suppress the chronic activation of microglia - a key cause of inflammation in the brain.(7-10)
                  • Brain Fog. Includes symptoms "reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory." According to researchers much of this is attributed to inflammation and microglial activation in particular. Luteolin, inhibits many steps in the inflammation process in the brain, and, may be effective in in ameliorating brain fog.(9)
                  • Neurogenesis. Apigenin induces neurogenesis by promoting neuronal differentiation of stem cells primarily in the hippocampus (the memory center).(11)
                  • Apigenin reverses inflammation induced depression in lab animals. Effectively attenuated by apigenin were proinflammatory cytokines IL-1β (interleukin-1β) and TNF-α (tumor necrosis factor-α). (12)
                  • Protects neurovascular coupling. Apigenin maintains neurovascular coupling. This is an important relationship between the neurons and the vascular network in the brain. Maintenance of brain health depends on the ability to preserve and increase cerebral blood flow and oxygenation. Termed "white matter hypersensities" are the areas of the brain which developed micro vascular deficiencies, lack of blood flow, causing loss of neuro function. (13)

                     Immune System

                    • Immune Allergic Response. Mast cells are primary to the immune allergic response which then releases a potent inflammatory response. Luteolin exhibits a modulatory effect on mast cell induced inflammatory response. (14) 
                    • Immunity Balanced Restoration. Inflammation disrupts the balance of the immune system function. Apigenin via an effective anti-inflammatory response, is capable of restoring  the immune response.(15)

                      Anti-Cancer

                      • Both apigenin and luteolin display potent ant-cancer properties.
                      • Apigenin:
                        • Prostate Cancer Cells. Studies indicate that apigenin may inhibit the progression of prostate cancer including tumor growth and invasiveness. (16)
                        • Colorectal Cancer Cells. Treated human colorectal cancer cells with apigenin, with extended exposure,  resulted in senescence of the cancer cells and attenuation of tumor formation. (17)
                        • Cancer Stem Cells. Apigenin inhibits the stimulation and self renewal of ovarian cancer stem cells.(18)  Furthermore, apigenin may inhibit other cancer stem cells via inhibition of the same chemical promoter (casein kinase 2α) thereby inhibiting other cancer stem cell self-renewal.(19)
                      • Luteolin:
                        • Anti-angiogenic - Cancer tumors grow by the creation of new bloods vessels, a process called angiogenesis. Luteolin inhibits the growth of new blood vessels in tumors.(20)
                        • Cancer Stem Cells.  Certain breast cancers have a high rate of recurrence due to the continued growth from cancer stem cells. Research indicates that luteolin blocks the pathway for cancer stem cell maintenance and may eliminate cancer stem cells.(21)
                        • Non-Small Cell Lung Cancer - Lab studies (in vitro) demonstrated the ability of luteolin to cause the cellular death of the cancer cells as well as inhibit migration.(22)

                        Anti-Diabetic Activity

                        • Apigenin and luteolin both inhibit gluconeogenic (glucose producing) and lipogenic (fat producing) gene expression.(23) 
                        • Apigenin improves glucose and lipid homeostasis.

                          Skin Rejuvenation

                          • Apigenin induces dermal collagen production, thereby serving as a potential agent improving collagen depleted skin. Collagen provides skin with youthful structure. Wrinkles are skin aging are the result of the loss of the collagen infrastructure.(24)

                            Hypertension

                            • Hypertension and low grade inflammation. Specifically, the link involves TLR4 - a protein involved with activation of  the innate immune response. Research indicates that TLR4 inflammatory response is key in the development and maintenance of hypertension.
                            • Apigenin was shown to significantly lower blood pressure in hypertensive rats, as well lowering inflammation, including reducing expression of TLR4 and inflammatory NF-KB and TNF-alpha.(25).

                                 

                                YELLOW LONGEVITY  (15 mg Apigenin plus 15mg Luteolin)

                                YELLOW NATURALLY  (10 mg Apigenin plus 10 mg Luteolin)

                                LONGEVITY NATURALLY (10 mg Apigenin plus 10 mg Luteolin)

                                CARTILAGE MAX (15 mg Apigenin plus 15 mg Luteolin)

                                  

                                REFERENCES:

                                1. Escande C, et al. Flavonoid Apigenin Is an Inhibitor of the NAD(+)ase CD38. Diabetes. 2013 Apr.

                                2. Braidy N, et al. Mapping NAD(+) metabolism in the brain of ageing Wistar rats: potential targets for influencing brain senescence. Biogerontology. 2014 Apr;

                                3. Blackwell TK, et al. SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med. 2015 Aug.

                                4. Paredes-Gonzalez X, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos. 2015 Apr 

                                5. Wang Q, et al. Inhibition of autophagy ameliorates atherogenic inflammation by augmenting apigenin-induced macrophage apoptosis. Int Immunopharmacol. 2015 Jul;

                                6. Zeng P, et al. Apigenin Attenuates Atherogenesis through Inducing Macrophage Apoptosis via Inhibition of AKT Ser473 Phosphorylation and Downregulation of Plasminogen Activator Inhibitor-2. Oxid Med Cell Longev. 2015

                                7. Yuan Y, et al. Anti-inflammatory effects of Edaravone and Scutellarin in activated microglia in experimentally induced ischemia injury in rats and in BV-2 microglia. BMC Neurosci. 2014 Nov

                                8. Wang S, et al. Neuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation. Neuroscience. 2011 Jun

                                9. Theoharides TC, et al. Brain "fog," inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin. Front Neurosci. 2015 Jul

                                10. Huang F, et al. The inhibitory effect of luteolin on inflammation in LPS-induced microglia. Zhong Yao Cai. 2011 Nov

                                11. Taupin P. Neurogenic drugs and compounds. Recent Pat CNS Drug Discov. 2010 Nov

                                12. Li R, et al. The effects of apigenin on lipopolysaccharide-induced depressive-like behavior in mice. Neurosci Lett. 2015 May

                                13. Liu R, et al. The flavonoid apigenin protects brain neurovascular coupling against amyloid-β₂₅₋₃₅-induced toxicity in mice. J Alzheimers Dis. 2011

                                14. Kritas SK, et al. Luteolin inhibits mast cell-mediated allergic inflammation. J Biol Regul Homeost Agents. 2013 Oct-Dec

                                15. Arango D, et al. Dietary apigenin reduces LPS-induced expression of miR-155 restoring immune balance during inflammation. Mol Nutr Food Res. 2015 Apr
                                16. Shukla S, et al. Apigenin blocks IKKα activation and suppresses prostate cancer progression. Oncotarget. 2015 Sep.

                                17. Banerjee K, et al. Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells. Redox Biol. 2015 Apr

                                18. Tang AQ, et al. Apigenin inhibits the self-renewal capacity of human ovarian cancer SKOV3‑derived sphere-forming cells. Mol Med Rep. 2015 Mar.

                                19. Liu J, et al. Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α. Mol Med Rep. 2015 Jan

                                20. Ambasta RK, et al. Comparative study of anti-angiogenic activities of luteolin, lectin and lupeol biomolecules .J Transl Med. 2015 Sep

                                21. Ma L, et al. Luteolin exerts an anticancer effect on NCI-H460 human non-small cell lung cancer cells through the induction of Sirt1-mediated apoptosis. Mol Med Rep. 2015 Sep

                                22. Davies AH, et al. Inhibition of RSK with the novel small-molecule inhibitor LJI308 overcomes chemoresistance by eliminating cancer stem cells. Oncotarget. 2015 Aug

                                23. Bumke-Vogt C, et al. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells. PLoS One. 2014 Aug 

                                24 Zhang Y, et al. Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway. Eur J Histochem. 2015 Apr 

                                25. Chen X, et al. Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B. Mediators Inflamm. 2013

                                Citrus Bergamot - the Small Italian Citrus with Very Big Cardiovascular Benefits

                                Ideal Natural Cardiovascular Support. If there were an ideal natural support ingredient for cardiovascular health it would include the following:

                                  • Significantly increase HDL
                                  •  Lower triglycerides
                                  •  Lower blood sugar
                                  •  Decrease LDL - most importantly the small VLDL (very-  low density  lipoprotein) 
                                  •  Also avoid the significant side effects of statin drugs.

                                    Contrary to the opinions of many doctors, cholesterol is essential for health and life! Furthermore, the larger sized LDL may not have a significant effect on cardiovascular health (with balanced HDL levels). In fact, larger LDL is essential for the function of the body, including cell membranes, synaptic junctions in the brain, and production of Vitamin D and sex hormones and should not be significantly reduced. VLDL, however is dangerous. It is a carrier of both triglycerides and cholesterol and easily infiltrates and damages the lining of the artery and accelerates atherosclerosis. High levels of VLDL are correlated with high triglycerides and coronary artery disease.

                                    Nearly perfect. Bergamonte® is the proprietary extract of Bergamot and virtually meets all the criteria for an ideal supplement for cardiovascular health.

                                    At a dose of 500mg per day (preferably before meals), in several major clinical studies involving patients with hyperlipemia, hypercholesterol  or metabolic syndrome, Bergamonte® was shown to have the following affects:

                                    • reduced total Cholesterol 22% 
                                    • increased HDL 22%
                                    • reduced LDL 24%
                                    • increased large LDL (30%) / decreased small dense VLDL (30%) 
                                    • reduced triglycerides 30%
                                    • reduced blood glucose 19%

                                    VASCULAR STRENGTH

                                     

                                    REFERENCES:

                                    (1) HP Ingredients research 2015

                                     Bergamonte® is a registered trademark of HP Ingredients

                                    Taurine - For Quality Longevity

                                    In a study from Japan, higher levels of dietary taurine was identified as the main factor attributing to the longer lifespan of the of the Japanese people.(1) Since then research has validated that taurine plays a major role in not only longevity, but quality longevity. Taurine plays a crucial role in most every system in the body and is considered an essential supplement for healthy aging.

                                     

                                    • Longevity - Taurine has been shown in studies of human populations (Japanese) as well as in research animals to extend longevity via decreased cellular senescence. An important longevity mechanism by taurine is by improving cellular protein folding, thereby stabilizing cellular protein homeostasis. (2,3) Loss of protein homeostasis (proteostasis) is considered a key characteristic of aging and is one of the earliest molecular changes seen in aging.(4)
                                    • Resistance to Injury.  Taurine provides protection against injury due to stress and disease. (2)
                                    • Brain Neurogenesis. In the brain, taurine stimulates the generation of new neurons in the hippocampus memory center(6). Furthermore, research indicates an enhanced duration of synaptic transmission.(7)
                                    • Mitochondria Function.   Taurine plays a significant role in mitochondrial function.and is essential to the mitochondrial matrix.(8)  In taurine deficient cells (importantly heart cells) mitochondria become severely damaged. Protein homeostasis and autophagy becomes dysfunctional. As a result, mitochondrial ATP production is reduced and oxidative stress (superoxide radicals) are increased.
                                    • Improves Testicular Function.  Taurine improves testicular function in aged lab animals and suppresses deterioration.(5)
                                    • Diabetes Health in Prevention and Therapeutic Effects. Diabetes is a condition which is characterized by high levels of oxidative stress, including chronic inflammation, which is responsible for resulting pathologiesTaurine has been shown to be effective in modifying the effects of these pathologies in both experimental and human studies.(10)  Taurine is also a regulator of glucose homeostasis and maintenance of the beta cells of the pancreas, preserving pancreatic function. (11) Supplementation of taurine to young type 1 diabetic men reversed arterial stiffness, and endothelium dysfunction, after only two weeks of 1.5 gm daily intake. (12)
                                    • Vascular and heart - Most importantly, taurine strengthens the heart muscle and contraction ability.In taurine deficient hearts, there is weakening and resulting cardiomyopathy, losing function (leading to heart failure).(15) Furthermore, taurine insufficiency is marked by systolic and diastolic defects(9),. Since taurine is so important for heart function, researchers suggest that stronger heart function may be a key component of taurine;s ability to increase longevity.(10) In addition to the heart, taurine supports the suppression of the development of atherosclerosis.(11)
                                    • Retinal (eye) health and function.  Taurine is the most abundant amino acid in the retina and plays the most significant role, Taurine is believed to be involved in the prevention of diseases involved with retinal degeneration. Furthermore, taurine supports survival of retinal ganglion (loss of ganglion is involved in the progression of glaucoma and diabetic retinopathy). (16,17.18) Cone photoreceptors and retinal ganglion cells are most susceptible to taurine deficiency.(19)
                                    • Exercise. Longer and stronger. Taurine enables muscles to contract harder and stronger - providing more effective workouts as well as an increased edge in athletic competition. Normal levels of taurine are required for normal muscle function. (20,21) According to the study, taurine levels "above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle". (21) Fast twitch muscle is the muscle involved in power activity, the exercise movements that are power driven (plyometrics, sprinting, heavy weight lifting). Cyclists training sessions have been longer with less fatigue, in part due to decreased oxidative stress and lactic acid.(22)
                                    • Elite athletes have both strong skeletal and cardiac muscle. Taurine increases muscle power (contraction) in both skeletal and cardiac muscle. (23) Stronger cardiac functionality increases oxygenation of skeletal muscle thus enabling stronger exercise performance (aerobic and anaerobic). In endurance exercises, taurine reduced muscle fatigue allowing for longer exercise. (24) Also reduces muscle inflammation and cellular damage during heavy exercise.(25)

                                    Normal dietary intake of taurine is quite low, normally ranging between 40mg - 400mg. Clinical studies indicate the need for up to 3,000mg (or more) to make significant health improvements and promote longevity.

                                    LONGEVITY NATURALLY (3000 mg of Taurine per serving)

                                    VISION VITALITY (800 mg of Taurine per serving)

                                    VASCULAR STRENGTH (500 mg of Taurine per serving)


                                    REFERENCES

                                    (1) Yamori Y, et al. Taurine as the nutritional factor for the longevity of the Japanese revealed by a world-wide epidemiological survey. Adv Exp Med Biol. 2009
                                    (2) Ito T, et al. Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PLoS One. 2014 Sep 17
                                    (3) Ito T, et al. Potential Anti-aging Role of Taurine via Proper Protein Folding: A Study from Taurine Transporter Knockout Mouse. Adv Exp Med Biol. 2015
                                    (4) Labbadia J, et al. Proteostasis and longevity: when does aging really begin? F1000Prime Rep. 2014 Feb
                                    (5) Yang J, et al. Taurine increases testicular function in aged rats by inhibiting oxidative stress and apoptosis. Amino Acids. 2015 Aug.
                                    (6) Gebara E, et al. Taurine increases hippocampal neurogenesis in aging mice. Stem Cell Res. 2015 May
                                    (7) Sergeeva OA, et al. aurine-induced long-lasting enhancement of synaptic transmission in mice: role of transporters. J Physiol. 2003 Aug
                                    (8) Hansen SH, et al. Taurine and regulation of mitochondrial metabolism. Adv Exp Med Biol. 2015;
                                    (9) Jong CJ, et al. The ubiquitin-proteasome system and autophagy are defective in the taurine-deficient heart. Amino Acids 2015 Jul 21.
                                    (10) Schaffer SW, et al. Does taurine prolong lifespan by improving heart function? Adv Exp Med Biol. 2015;
                                    (11) Murakami S. Taurine and atherosclerosis. Amino Acids. 2014.
                                    (12) Sirdah MM. Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation. Diabetes Metab Syndr 2015 Jan-Mar;
                                    (13) Dantos-Silva JC, et al. Taurine supplementation ameliorates glucose homeostasis, prevents insulin and glucogon hypersecretion, and controls Beta, alpha and gamma masses in genetic obese mice. Amino Acids. 2015 Aug;
                                    (14) Moloney MA, et al. Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics. Diab Vasc Dis Res. 2010 Oct
                                    (15) Ramila KC, et al. Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts. Am J Physiol Heart Circ Physiol. 2015 Feb
                                    (16) Heller-Stilb B, et al. Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J. 2002 Feb
                                    (17) Froger N, et al. Taurine: the comeback of a neutraceutical in the prevention of retinal degenerations. Prog Retin Eye Res. 2014 Jul.
                                    (18) Froger N, et al. Taurine is a crucial factor to preserve retinal ganglion cell survival. Adv Exp Med Biol. 2013.
                                    (19) Gaucher D, et al. Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells. Amino Acids. 2012.
                                    (20) Spriet LL, et al. Taurine and skeletal muscle function. Curr Opin Clin Nutr Metab Care. 2015 Jan;
                                    (21) Goodman CA, Horvath D, Stathis C, et al. Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation.J Appl Physiol.2009 Jul.
                                    (22) Zhang M, et al. Role of taurine supplementation to prevent exercise-induced oxidative stress in healthy young men. Amino Acids, 2004.
                                    (23) Manabe S, et al. Decreased blood levels of lactic acid and urinary excretion of 3-methylhistidine after exercise by chronic taurinetreatment in rats
                                    (24) Yatabe Y, et al. Effects of taurine administration on exercise. Adv Exp Med Biol. 2009;
                                    (25) Kato T, et al. The effects of taurine administration against inflammation in heavily exercised skeletal muscle of rats. Adv Exp Med Biol. 2015.

                                    Resveratrol and Pterostilbene - miRNA the New Target for Prostate Cancer

                                    New research suggests that miRNA (microRNA) is a new target in the war against prostate cancer. MiRNA are short segments of RNA but are not involved with the coding of protein. However, miRNA does play a role in gene expression, frequently to silence the expression of a gene. In the case of prostate cancer, miRNA silences the expression of a tumor suppression protein, thereby allowing growth of the prostate cancer. Resveratrol and pterostilbene increases expression of the tumor suppression protein by decreasing levels of miRNA, thereby suppressing prostate cancer growth. Authors of the new research suggest that both stilbenes (resveratrol and pterostilbene) as candidates for chemopreventive and therapeutic use in prostate cancer.

                                    PURPLE LONGEVITY


                                    REFERENCES:

                                    (1) Dhar S, et al. Resveratrol and pterostilbene epigenetically restore PTEN expression by targeting oncomiRs of the miR-17 family in prostate cancer. Oncotarget. 2015 Aug 6

                                    September 06, 2015

                                    Posted in Fibrosis Organ Scarring Nrf2


                                    Aging inside the body: Internal Organ Scarring & Natural Nrf2 Protection

                                    Longevity requires the continued optimal functioning of organs in the body, including heart, lungs, liver and pancreas. Injury and inflammation causes damage to organs, and the body attempts repair by laying down fibrotic tissue (scar tissue) to heal the damage. This process of fibrosis results in non-functional scar tissue being applied to a critical organ. In younger people, the scar tissue is eventually replaced with functional tissue. However, with age, this recovery process becomes compromised, and scar tissue remains, disrupting the ability of the organ to function. Over time scar tissue can accumulate and further inhibits the normal function of the organ.

                                    Scar tissue which accumulates in the heart, lungs, kidneys or liver can result in devastating effects and even lead to death. Pulmonary fibrosis, for example, resulting from smoking or environmental factors progressively scar the lung until the person can no longer breath, and the disease is fatal. Aging of the heart is associated with fibrotic scars, which can lead to atrial fibrillation and decreased capacity of the heart to function.Cirrhosis of the liver is scarring of the liver, from chronic inflammation, which leads to liver failure.

                                    • Aging is considered a risk factor for increased fibrosis, in addition to external factors and inflammation (which incurs a systemic increase with age).
                                    • A report from the University of Alabama estimates that human fibrotic disorders contribute to 45 percent of deaths in the United States.
                                    • Nrf2 is a powerful transcription factor which is activated within the body and regulates antioxdant proteins which protects against the oxidative stress incurred by injury and inflammation. Research suggests that dysfunctional nrf2 levels (lower levels) may play a significant role in fibrosis formation. Experiments with mice with deficient levels of Nrf2 experienced more severe fibrosis and scarring. Increasing activation of Nrf2 is considered an important strategy in reducing fibrosis and the scarring of organs within the body.


                                    Natural Nrf2 activators include sulforaphane (derived from glucoraphanin), curcumin, andrographolide, n-acetyl-cysteine, anthocyanins, C3G (anthocyanin), rosemary (carnosic acid), resveratrol, pterostilbene, baicalin, apigenin, luteolin

                                    XGEVITY
                                    AIR VITALITY
                                    PURPLE LONGEVITY
                                    BLUE NATURALLY
                                    CURCUMIN XTRA-MAX / YELLOW LONGEVITY

                                    LONGEVITY NATURALLY


                                    REFERENCES:

                                    (1) Hecker L, et al. Reversal of persistent fibrosis in aging by targeting Nox4-Nrf2 redox imbalance. Sci Transl Med. 2014 Apr.
                                    (2) Zhao YY, et al. Metabolomics analysis reveals the association between lipid abnormalities and oxidative stress, inflammation, fibrosis, and Nrf2 dysfunction in aristolochic acid-induced nephropathy. Sci Rep. 2015 Aug 7
                                    (3) Ni S, et al. Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling. Int J Clin Exp Pathol. 2015 Jul 1
                                    (4) Zhang Z, et al. Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway.
                                    (5) Dzeshka MS, et al. Cardiac Fibrosis in Patients With Atrial Fibrillation: Mechanisms and Clinical Implications. J Am Coll Cardiol. 2015 Aug 25
                                    (6) Lee TY, et al. Modulation of thioacetamide-induced hepatic inflammations, angiogenesis and fibrosis by andrographolide in mice. J Ethnopharmacol. 2014 Dec 2
                                    (7) Aboonabi A, et al. Chemopreventive role of anthocyanins in atherosclerosis via activation of Nrf2-ARE as an indicator and modulator of redox. Biomed Pharmacother. 2015 May
                                    (8) Speciale A, et al. Cyanidin-3-O-glucoside (C3G) counters the response to TNF-alpha of endothelial cells by activating Nrf2 pathway. Mol Nutr Food Res. 2013 Nov.
                                    (9) Paredes-Gonzalez X, et al. Induction of NRF2-mediated gene expression by dietary phytochemical flavones apigenin and luteolin. Biopharm Drug Dispos. 2015 Apr 22.