Anti Aging Drug Breakthrough Achieved

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Publishing his work in the prestigious journal Science, David Sinclair of Harvard reports a breakthrough in the development of drugs that can block the aging process.

The article is entitled Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators, and reveals how interaction with a single amino acid in the SIRT1 enzyme is crucial for the ability of drugs that can activate the enzyme.

SIRT1 is an enzyme in the class of molecules called Sirtuins. Significant research shows that activation of sirtuins  reduces cellular aging through its interaction with other cellular master switches such as FOXO3a and PGC-1a

“At the cellular level,” explain the authors. “SIRT1 controls DNA repair and apoptosis, circadian clocks, inflammatory pathways, insulin secretion, and mitochondrial biogenesis”

Resveratrol a polyphenol found in red wine and grapes may be a weak natural activator of sirutin and has been linked in some studies with the extension of animal lifespan. Data on these sitruin activators or STACs is inconsistent. “The legitimacy of STACs as direct SIRT1 activators has been widely debated,” write the authors.

In the present study, the researchers developed a sirtuin  activation assay. They tested 117 experimental STACs and were able to prove that the enzyme could be directly activated and uncovered the exact molecular  mechanism by which this occurred.

The authors conclude:

The data presented here favor a mechanism of direct “assisted allosteric activation” mediated by an N-terminal activation domain in SIRT1 that is responsible for at least some of the physiological effects of STACs. Thus, allosteric activation of SIRT1 by STACs remains a viable therapeutic intervention strategy for many diseases associated with aging.

“Ultimately, these drugs would treat one disease, but unlike drugs of today, they would prevent 20 others,” says Sinclair, from Harvard University. “In effect, they would slow ageing.” He points out this research shows something never previously described ”In the history of pharmaceuticals, there has never been a drug that tweaks an enzyme to make it run faster,” he said.

From this work, Sinclair  believes safe new drugs of this class could be available in as little as five years. There will still be the need to prove their effectiveness.

“Now we are looking at whether there are benefits for those who are already healthy. Things there are also looking promising,” he says. ”We’re finding that ageing isn’t the irreversible affliction that we thought it was,”

“Some of us could live to 150, but we won’t get there without more research,” he adds.

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11 Responses to “Anti Aging Drug Breakthrough Achieved”

  1. Ed Evans says:

    If you are in need of discreet human test subjects. I am surely your man.

  2. [...] Source: http://extremelongevity.net/2013/03/08/anti-aging-drug-breakthrough-acheived/ Print / Email Social Share [...]

  3. Steven Dobbie says:

    Sign me up and send some to Scotland asap xD

  4. Michael says:

    I am afraid that I can’t agree that this is a breakthrough of any sort. The study may resolve the debate over whether resveratrol and its analogs that the drugs hit their ostensible molecular target (and I’ve not formed a judgement on the question), but the question is what if anything this means for their effects on degenerative aging and age-related disease.

    Back when there was some reason to think that sirtuin activation might slow the aging process, this would have been an exciting result. But resveratrol has now been tested at six different doses in normal, healthy mice, and one dose in rats, and has not extended the lifespan of mice that aren’t diabetic and obese by a single day.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021372/
    (If the screen comes up blank and grey, scroll down).
    http://www.ncbi.nlm.nih.gov/pubmed/22451473
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2538685
    http://www.ncbi.nlm.nih.gov/pubmed/22818625

    It’s also failed to demonstrate even short-term metabolic benefits in normal, healthy humans (eg,
    http://www.ncbi.nlm.nih.gov/pubmed/23102619

    … although there have been some benefits seen in very overweight or obese and/or diabetic or borderline-diabetic subjects in some studies (and even that hasn’t been consistent — eg:
    http://diabetes.diabetesjournals.org/content/early/2012/11/19/db12-0975.abstract

    Moreover, even boosting sirtuin activity directly, by giving mice an extra dose of the gene, has no effect on lifespan (though it did have some health benefits):
    http://www.nature.com/ncomms/journal/v1/n1/abs/ncomms1001.html

    So whether resveratrol or its anlogs boost SIRT1 activity, this study isn’t a breakthrough: a breakthrough would be to show that they can extend the healthy lifespan of normal, healthy mammals.

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