Can Sirtuins Block The Aging Process?

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.

Sinclair believes that safe drugs of this class could be available for testing in as little as five years.

Mankind has wished for a Fountain of Youth for a long time. Science fiction writers have expressed their longing for a scientific basis to anti-aging. One such example is the Sprung-Samser treatment from Roger Zelazny's 1966 novel This Immortal:

Eighty or ninety or more, looking about forty, [Hasan] could still act thirty. the Sprung-Samser treatments had found highly responsive material. It's not often that way. Almost never, in fact. They put some people into accelerated anaphylactic shock for no apparent reason, and even an intracardial blast of adrenalin won't haul them back; others, most others, they freeze at five or six decades. But some rare ones actually grow younger when they take the series - about one in a hundred thousand.

Fans of the Cities in Flight novels by James Blish may recall the anti-agathic drugs that were provided to a select few members of the cities.

From Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators via Extreme Longevity.

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