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  • Seven Evidences LONGEVINEX® Works To Promote Longevity In Living Cells (parts 5 & 6)

    November 17, 2014: by Bill Sardi

    You can read parts 1 and 2 here >>
    You can read parts 3 and 4 here >>

    5. Longevinex provides ingredients that activate KLOTHO anti-aging gene.

    In the wake of a decade that ushered in excitement over the prospect that activation of a single gene, Sirtuin1, could extend the lives of humans, a relatively new anti-aging gene was overlooked. It is called the KLOTHO gene (KLOTHO from the Greek goddess who spins the thread of life). The lifespan of KLOTHO-deficient mice is only 5-6% of that of healthy mice. [Science Aging Knowledge Environment 2006] On the other hand, mice that over-produce KLOTHO gene protein live 20-30% longer. The mechanism for this life extension is derived from the ability of KLOTHO to inhibit insulin and Insulin Growth Factor-1 signaling. [Science 2005]

    Two ingredients in Longevinex® are reported to increase KLOTHO gene activity. Consistent with the over-mineralization theory of aging, vitamin D that activates the KLOTHO gene, controls calcium and phosphate in the human body. [Advances Experimental Medicine Biology 2012]

    Resveratrol working directly in the kidney [International Journal Biochemistry Cell Biology Aug 2014], and also by indirect methods, increases KLOTHO by increasing vitamin D receptor protein. [Journal Steroid Biochemical Molecular Biology Feb 2003] Resveratrol works synergistically with vitamin D and KLOTHO. [Molecular Nutrition Food Research March 2014; Vitamin D Oxidative Stress & Immune Aging, CRC Press 2013]

    More extensive reports about the KLOTHO gene and longevity can be found elsewhere. [Knowledge of Health Oct 19, 2012; May 15, 2014]

    6. Inhibition of the hypoxia signal

    The strongest evidence that separates Longevinex® from the biological activity produced by generic resveratrol it is its ability to control the master regulator of oxygen homeostasis (normalcy) called Hypoxia Inducing Factor-1 (HIF-1). [Molecular Pharmacology May 2014]

    MicroRNA-20b is the master controller of HIF-1. [Journal Cellular Physiology July 2010] In a study conducted by National Institutes of Health researchers, resveratrol was found to down-regulate HIF-1 via microRNA-20b -189 fold, Longevinex® -1366 fold (a six times difference). [PLoS One Dec 23, 2010]

    Remarkably, HIF-1 controls many important biological processes.

    • HIF-1 controls the signal that cells are deprived of oxygen and therefore need to convert to using sugar instead of oxygen for energy. [Asia Pacific Journal Clinical Nutrition 2014]
    • HIF-1 synthesis triggers the development of abnormal blood vessels (angiogenesis or neovascularization) that can damage the eyes and kidneys.
    • HIF-1 is the primary signal required for antioxidant defenses to be activated in heart tissue prior to a heart attack (called cardiac preconditioning). [Proceedings National Academy Science Oct 22, 2013]
    • Genetic inhibition of HIF-1 suppresses the effects of a high-fat diet in fatty (adipose) tissue and induces reduction of weight gain in laboratory animals given a high-fat diet. [Molecular Cell Biology March 2013]
    • In diet-induced diabetes accompanied by obesity, HIF-1 is the biological signal that induces hearing loss. [PLoS One April 26 2014]
    • Inhibition of HIF-1 spares tissues at the back of the eye from damage caused by invasion of new blood vessels (angiogenesis, neovascularization). [Advances Experimental Medicine Biology 2014; Aging Research Review Oct 2009]
    • Elevated HIF-1 levels serve as a marker for calcification of coronary arteries. [Cardiovascular Diabetology Feb 24, 2014]
    • In concert with the over-mineralization theory of aging, following oxygen deprivation (hypoxia) tissues sequester excess iron and therefore HIF-1 inhibition may limit the accumulation of iron in tissues damaged by poor circulation. [Neuropharmacology Feb 2014]
    • The primary use of sugar for cellular energy is how cells are characterized as being cancerous. [Bio-organizational Medicinal Chemistry Letter Sept 20, 2014] Inhibition of HIF-1 not only thwarts the initial step in the genesis of tumor cells HIF-1 inhibition also blocks the spread (metastasis) of tumors. [Science Reports Jan 23, 2014] Resveratrol has been demonstrated to suppress the use of sugar for energy by cancer cells via HIF-1 inhibition [Journal Nuclear Medicine Dec 2013]

    While more sophisticated and costly methods of HIF-1 inhibition have been demonstrated in the laboratory [PLoS One 2012] the use of small natural molecules, in particular polyphenols found in grapes, olives, tea leaves and spices may be a more practical alternative. [Current Medicinal Chemistry 2011]

    The HIF-1/Resveratrol paradoxes

    Despite the fact HIF-1 is required for cardio-protection [Proceedings National Academy Science June 26, 2012], with Longevinex® being the strongest natural anti-HIF-1 inhibitor ever tested [PLoS One Dec 23, 2010], resveratrol and more so Longevinex® still exhibit ability to protect the heart from damage produced by heart attacks (interruption of oxygen supply to heart muscle). [PLoS One Dec 23, 2010]

    More remarkable, resveratrol simultaneously inhibits new blood vessels that threaten loss of vision at the back of the eyes while encouraging the development of new blood vessels in a damaged heart. [Aging Diseases April 1, 2014; Journal Molecular Cell Cardiology Nov 2005]

    Similarly, the medulla of the kidneys is chronically oxygen deprived (state of hypoxia) due to its constant water fluid bath. HIF-1 is required to prevent damage to the kidneys. [Kidney International 2005] However, resveratrol, an HIF-1 inhibitor, protects kidney function. [Journal Clinical Investigation April 2010]

    In another paradox, the expression of the HIF-1 gene protein is required to induce stem cells from fibroblasts in a lab dish. [Journal Integrative Medicine Nov 2013] Transfused stem cells generally do not survive beyond 24-72 hours. But even though resveratrol is known to inhibit HIF-1, instillation of resveratrol prior to transfusion of cardiac stem cells results in stem cell survival. [Journal Cellular Molecular Medicine Jan 2012]

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