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  • Road To Longevity: Wrong Gene, Right Molecule

    September 22, 2011: by Bill Sardi

    Nothing new here, we’ve discussed this a couple of times in prior reports, that the road to longevity is not dependent upon a single gene, nor solely upon the Sirtuin1 survival gene, and it doesn’t require 1000 bottles of red wine to produce the same positive biological effects seen in the animal lab. But red-wine resveratrol pills are back in the headlines again today for yet another round of scientific scrutiny

    “It turns out, the researchers who brought us to the longevity party may have had the wrong gene target in mind and maybe the elixir for perpetual youth is more of a low-octane mixed drink closer to that found in red wine rather than plain resveratrol juice, but we need to recognize there was no scientific or public interest in longevity pills till 2001 when MIT and Harvard researchers first identified a key gene that is activated when living organisms are placed on a limit calorie diet,” says Bill Sardi, spokesperson for Longevinex®, a leading maker of resveratrol pills.

    “We can’t fault the researchers. They brought us all to the party. It’s just that when the smoke cleared, some flaws in the science now show that when the SIR2 gene (akin to the Sirtuin1 survival gene in humans) is removed from fruit flies, their lives are still significantly extended,” says Sardi. Conclusion: wrong gene target.

    In a second experiment, when a prior study that employed a limited calorie diet was repeated in roundworms, only this time with a more commonly-found strain of nematodes rather than a mutated strain, life extension dwindles down from a first-quoted 15-50% to just 10-15%. It was not realized at the time that a mutated strain of roundworms would skew the results of a longevity study.

    Leonard Guarente of MIT, the researcher who made the initial discovery linking Sir2 (Sirtuin1 in humans) to calorie restriction, maintains the gene target is correct it is just the amount of life extension that is in question.

    He says the new findings are nothing more than a minor technical blip. An article in MIT’s Technology Review quotes Guarente to say: “It was a problem with the strain, and that has been fixed. It does not invalidate the conclusions.” Guarente goes on to say that other labs have since replicated the link between Sir2 and longevity and have shown a 20 percent increase in lifespan in worms using newer methodology.

    But 20% life extension is not the consistent doubling of lifespan that is commonly achieved with a calorie restricted diet in many life forms. Anything that solely targets Sirtuin1 is not a true mimic of calorie restriction.

    A rodent study conducted in 2008, published in Experimental Gerontology, sheds more light on the subject. Long-term calorie restriction has been shown to significantly differentiate 831 genes in laboratory rats. A short-term experiment was conducted over a period of 12 weeks to determine to what extent and how rapidly resveratrol resembles the gene activation pattern of calorie restriction. The limited calorie diet altered 198 genes while low-dose resveratrol switched about the same number of genes (225). But when a matrix of small molecules (Longevinex®) designed to replicate the effects of red wine was used, 1711 genes were significantly changed in the short-term, and 677 of the 831 longevity genes in this species were switched in the same direction as calorie restriction. That is the closest thing to a molecular mimic of a calorie-restricted diet in animals that has been tested to date.

    This experiment suggests it would require life-long adherence to a limited calorie diet or consumption of plain resveratrol to achieve the same gene pattern in long-lived rodents. However, when a matrix of low-dose small molecules was employed, the beneficial effects were realized within weeks. Consumers of plain resveratrol pills may experience health benefits but not all the longevity properties that this molecule delivers.

    GlaxoSmithKline, the British-based pharmaceutical giant that purchased SRT501, a resveratrol-based developmental drug from Sirtris Pharmaceuticals for $720 million, seems to be talking out of two sides of its mouth. A statement by GSK says: “These two publications in lower-order species do not have any direct impact on the understanding of the role of sirtuins in human health and disease nor in our drug discovery efforts targeting these enzymes.” But the resveratrol-based SRT501 drug owned by GSK has been abandoned, despite all its promise.

    Before you throw away your resveratrol pills, investigate these facts:

    1. Resveratrol protects the heart prior to a heart attack, the only agent that has been found to do this, and turns mortal heart attacks into non-mortal events in animal experiments.
    2. Resveratrol simultaneously removes cholesterol from the liver and beta amyloid plaque from the brain.
    3. Resveratrol has anti-cancer properties independent of the Sirtuin1 gene and is considered the most promising anti-cancer molecule on the planet.
    4. Some people suffering with an unremitting form of macular degeneration, even with the most current medicines, are beginning to find a resveratrol-based pill may bring back their lost sight.
    5. The longevity pathway may actually begin with another Sirtuin family gene – Sirtuin3.

    Strikingly, none of this change in the science has altered what most of the 345 resveratrol pill makers claim about their products – that the ingredients in their products activate the Sirtuin1 survival gene. “Most of these resveratrol pill companies have no scientific background and are only profiteering off of old and now outdated science,” says Sardi. #### © 2011 Bill Sardi, Not for posting on other websites.

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