May 18, 2004

Yes SIR2!

Here's a quick recap: caloric restriction leads to longevity in virtually every animal species in which it's been tried. Why? There is continuing debate, but a lot of attention has been given to an enzyme, SIR2, that is increased with caloric restriction.

When Phil first reported on the enzyme SIR2, he was cautiously optimistic:

This is good news, but these are early results. First off, the findings apply only to yeast. (Although it can be surprising to learn how closely related we humans are to what we would normally consider much lower forms of life.) Secondly, we're a long way from finding a way to increase SIR2 levels without the rabbit-food regimen.

I love it when accelerating change takes even we Speculists by surprise:

Marmorstein and colleagues [researchers at the The Wistar Institute in Philadelphia] found that sirtuins [a family of enzymes that includes SIR2] influence longevity by flipping genetic switches. They appear to promote genomic stability, a process that goes awry in cancer and aging.

This is important. Just because something follows, it does not mean that it's the cause. We knew that SIR2 levels increased prior to measurable increases in longevity, but that did not mean that SIR2 was the reason. Now that we have a greater understanding of what SIR2 does, we may soon be able to evaluate SIR2's involvement in regulating lifespan.

But wait, there's more:

[Marmorstein and colleagues] used a yeast sirtuin as a model and captured 3D images of it to gain a structural picture of its enzymatic activity.

This led them to a binding site that when blocked activated the sirtuin.

Using virtual libraries of molecules, they are now identifying molecules with structures that might bind to this site and serve as SIR2 activators.

I am just overcome with geeky joy reading stuff like this. Think about the tools that were required to take these three steps. These tools were simply not available ten years ago. And what if Marmostein's group is correct about SIR2?

Okay, I'm back in control. "This is good news, but these are early results."

Posted by Stephen Gordon at May 18, 2004 10:24 AM | TrackBack

Nicely done, Stephen. I hope they're right. Most people can't or won't tolerate calorie restriction. These may be early results but if they're on the right track, Marmostein's group will make the breakthrough soon enough for us to reap the benefits!

Posted by: Kathy at May 18, 2004 07:14 PM

Think simple. Learn different.

Posted by: John at July 5, 2004 11:24 PM
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