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Longevinex® Achieves Age Reversal Effect Via Alternate Gene Pathway

Late last year when biologists announced in the journal CELL that a niacin-like molecule restores energy to aged cells, reversing markers of aging akin to making a 60-year old human 20-years old again, the mechanism described was attention getting.

Slowing the rate of aging desirable, though such an accomplishment has limited utility among those who have already lived most of their lives. The idea of a pill that can not only slow but also reverse aging has captured the attention of noted inventor and futurist Ray Kurzweil. This discovery means it is never too late in life to address aging with anti-aging strategies.

The niacin-like drug used by biologists in their lab rat study was nicotinamide mononucleotide, a precursor to a molecule called nicotinamide adenine dinucleotide (NAD), said to cost $1000 per gram (1000 milligrams) and would cost $35,000 for a 190-lb. man.

The expensive niacin-like drug inhibits a gene called hypoxia inducing factor-1 (HIF-1), a gene that begins to spew out proteins that results in less and less production of cell energy. The result is that hearts beat weaker, skin wrinkles faster and brain performance is slower as HIF-1 gene-derived proteins progressively rise with advancing age.

HIF-1 protein disrupts communication between the nucleus of living cells, where most of the cell’s genetic material (DNA) is housed, and cellular energy-producing compartments called mitochondria. Mitochondria generate energy as adenotriphosphate (ATP). [Learn how to say adenotriphosphate correctly here.] By age 80 only 4% of mitochondria produce ATP cellular energy.

Over time a survival gene known as Sirtuin1 loses its ability to keep HIF-1 in check and cellular energy declines. This is where Longevinex® has application as it is a profound HIF-1 inhibitor.

National Institutes of Health researchers, reporting in the journal PLoS ONE in 2010, report that resveratrol hinders HIF-1 by a 6-fold inhibition of micro-RNA-20b, a master genetic controller of HIF-1, in rodent heart tissue. (Micro RNA is considered the “guiding hand” of the human library of genes.)

More remarkably, Longevinex® inhibits HIF-1 38-fold, or a 633% greater age-reversing effect. This means hearts should predictably beat stronger and the brain will react quicker and more responsively. This still has to undergo animal and human trials for confirmation, but researchers are heralding their own discovery and working feverishly to commercialize it based upon the sole animal study that was conducted.

As long as molecular communication between the cell nucleus and the mitochondria is maintained, cells stay  healthy. Longevinex® appears to exhibit a profound effect in that regard.

Prominence of Sirtuin3 gene in longevity

Longevinex® has another distinct advantage – it activates Sirtuin3 almost three times greater than the red wine molecule resveratrol, a gene that is connected with superlongevity in humans. [Arbitrary units: resveratrol 0.40, Longevinex®-based matrix 1.18 = +295% increase Sirtuin3 mitochondrial SOD activity. Source: Canadian Journal Physiology Pharmacology, Vol. 88, Page 1017, 2010]

The Sirtuin3 gene is convincingly qualified to address aging in the mitochondria whereas other more heralded survival genes Sirtuin1 are not operable in the mitochondria. Sirtuin3 works exclusively in the mitochondria and not the cell nucleus.

Since restriction of calories by 40-50% is widely known to double the healthspan and lifespan of most living organisms, the prospect of a pill that can mimic this effect was first introduced in 2003 when Harvard Medical School biologists linked a red wine molecule (resveratrol) with activation of the same gene (Sirtuin1) involved with calorie restricted diets.

But in the decade that has passed a growing body of evidence now points to another Sirtuin-family gene, Sirtuin3, as the best candidate to expand the human lifespan.

Consider these facts about the Sirtuin3 survival gene:

• The Sirtuin3 gene contributes to the repair of mitochondrial DNA (the mitochondria have their own genome (library of 13 genes, versus ~25,000 genes in the cell nucleus).
• Sirtuin3 gene proteins activate a protective internal antioxidant enzyme called superoxide dismutase-2 (SOD2) that helps repair broken DNA in stem cells. (Stem cells are undefined native cells that can differentiate to become new heart, brain or muscle cells in the process of cellular regeneration.) Sirtuin3 is considered “indispensable for human stem cell maintenance.”
• Sirtuin3 may be beneficial for maintaining human fertility, in averting premature or delayed ejaculation in males.
• Sirtuin3 gene-derived protein also mimics physical exercise.
• In fact, Sirtuin3 mimics aerobic interval training. (This is described as short periods of intense exercise followed by less aggressive rest or recovery periods to achieve the same effect as extensive and continuous exercise.)
• Sirtuin3 gene-derived protein is reduced in sedentary individuals but not endurance-trained individuals.
• Sirtuin3 gene protein is induced in the liver during fasting.
• Hearts that fail have lower amounts of Sirtuin3 gene-derived protein.
• Sirtuin3 counters aging changes induced by pre-diabetes in the male sex organs (testicles).
• Sirtuin3 helps maintain the protective skin barrier.
• Sirtuin3 gene protein helps to maintain muscle flexibility.
• Sirtuin3 gene-derived protein protects against starvation.
• Sirtuin3 gene-derived protein slows age-related hearing loss.
• Sirtuin3 gene-derived protein helps maintain insulin-secreting cells in the pancreas.
• Sirtuin3 gene-derived protein protects heart muscle cells from oxidation whereas nicotinamide, a niacin-like molecule, was found to increase damage to the heart.
• Sirtuin3 is a prominent regulator of the beneficial effects produced by a calorie restricted diet.
• Alarmingly, the anti-diabetic drug metformin, often panned as an anti-aging drug, reduces Sirtuin3 gene-derived protein.
• Over-production of Sirtuin3 gene-derived protein protects the brain.
• Sirtuin3 is considered the “key regulator of mitochondrial cell energy.”
• Tumors lacking Sirtuin3 gene-derived protein exhibit high levels of oxidation that results in increased levels of HIF-1.
• Remarkably, when eating a high-fat diet, the production of Sirtuin3 gene-derived protein is inhibited to restore metabolic balance.
• The loss of Sirtuin3 protein contributes to diabesity.
• Sirtuin3 protects against over-stimulation of brain cells (excitotoxicity).
• Mice bred so they do not produce any Sirtuin3 gene-derived protein show signs of accelerated aging and liver disease.
• Mice bred to produce no Sirtuin3 protein are less resistant to biological stress and more susceptible to an enlarged heart, a hallmark of aging.
• The protective life-prolonging effect of calorie restriction is diminished in mice lacking the Sirtuin3 gene and its Sirtuin-3 generated antioxidant SOD2.

The antioxidant theory of aging and Sirtuin3

Millions of Americans take supplemental antioxidants. One of the major drawbacks of antioxidant therapy is that the use of supplemental antioxidants may not specifically address oxidation in the mitochondria. Since the mitochondria account for 90% of the oxidation in the human body, the ineffectiveness of supplemental antioxidants may explain why the oxidative stress theory of aging proposed by Denham Harman in 1956 has never gained traction.

A potential explanation for this controversy has emerged from recent studies involving Sirtuin3. The Sirtuin3 gene improves the ability to activate a critical internal antioxidant enzyme called SOD2 which is considered a crucial mitochondrial antioxidant. In fact, SOD2 is not fully active without the participation of Sirtuin3.
It is possible that small molecule activators of Sirtuin3 (like Longevinex®) can extend the lifespan of laboratory animals and humans.

A recent journal article said this about Sirtuin3:

“Even though vaccination, antibiotics, better child care, and early disease-detection techniques in combination with modern drugs have helped us to increase our average lifespan, the quest to increase maximal lifespan still remains elusive. In a clinical study, it was reported that older individuals (60+ years) with a sedentary lifestyle had ~40% reduced SIRT3 levels when compared with younger subjects, and after endurance exercise, the health benefits of older patients were accompanied by elevated levels of SIRT3.

The heart produces and utilizes more energy than any other organ, and more than 90% of its energy is produced from mitochondrial respiration. Normal cardiac function is maintained only if ATP is continuously re-synthesized. To meet this high energy demand, heart muscle cells have the highest density of mitochondria among all mammalian organs and occupy ~30% of the heart volume.

SIRT3-deficient mice, who look normal in their routine activity, develop an enlarge heart and scarring at 8 weeks of age. Mice that are genetically altered to produce more Sirtuin3 blocks heart enlargement among mice genetically altered to over-produce Sirtuin3. Sirtuin3 deficient mice exhibit 30% reduced ATP levels and is considered “an important player in the regulation of cellular ATP levels.”

Researchers says “a strong case has been built for SIRT3 as a protector against the ravages of aging.” #### ©2014 Bill Sardi, ResveratrolNews.com