Sirtuins are Increasingly Looking Like a Dead End

Sirtuins are most likely a dead end, or more charitably a stepping stone for researchers seeking after the mechanisms that link natural variations in metabolism to natural variations in life span, especially those induced by the practice of calorie restriction. It was one of the earliest identified pieces of the puzzle, but possibly not a useful piece in the final analysis. This has become increasingly likely as an outcome over the years as meaningful results failed to emerge from drug development based on the manipulation of sirtuins. But this happens all the time: it's larger than usual news in the scientific community only, I think, because very large sums of money have moved into this line of research over the past years, and it's one of the earliest threads that might have led to drugs that modestly slowed aging.

Though I should note, as usual, that it is a massive strategic error for the research community to focus on undertaking expensive research programs that can - at best reasonable expectation - only produce a very modest slowing of aging after the usual couple of decades of work from early results to broadly available clinical application. That strategic error is, unfortunately, well entrenched and well underway. The real and important battle of the next decade is to convince the research community, on the merits of the proposal, to ditch work on metabolic manipulation in favor of SENS-like biological repair approaches that offer the possibility of actual, working, meaningful rejuvenation of the old at the end of an expensive, large-scale twenty year research program.

But back to sirtuins, which are today's news. Here are a couple of items for you from around the web:

Longevity Gene Debate Opens Trans-Atlantic Rift

the idea that sirtuins promote longevity appeals to scientists because of experiments that were started in yeast and repeated in two other standard laboratory organisms, the roundworm and the fruit fly. It is these foundation experiments that have now come under attack by David Gems and Linda Partridge, researchers on aging at University College London. In an article published Wednesday in the journal Nature, they and colleagues have re-examined experiments in which roundworms and flies, genetically manipulated to produce more sirtuin than normal, were reported to live longer. Both experiments were flawed, they say, because the worms and flies used as a control were not genetically identical to the test organisms. The London researchers report that they have repeated the experiments with proper controls and found that extra sirtuin does not, after all, make the worms or flies live longer.

Is The 'Longevity' Gene Sirtuin One Big Research Error?

And in the last decade, sirtuin has probably been one of the industry's biggest bets, ever since high levels of this protein were linked to longer, healthier lives in a variety of animals and it was suggested that they could be behind the increased longevity seen with calorie restriction (drastic restriction of calories, without malnutrition is known to increase longevity and retard age-related diseases). So how did we get here, 10 years on, concluding that it is all a mistake?

So it all goes. The bottom line for us is, however, that even if sirtuins were the key to replicating calorie restriction, they wouldn't be the basis of the future medicines of rejuvenation. Rejuvenation biotechnology can only be based on means of repairing the damage of aging, not changing metabolism a little to gently slow down aging. Other than the SENS Foundation, I don't see any research-focused organization seriously pushing this viewpoint at the present time. That's a big problem: it means that most of the money going into aging and longevity science will have little to no effect on the future of your life span: it will be going towards a continuation of the present trend that adds a small fraction of a year to the life expectancy of adults with each passing year. The newborns get a bigger fraction of a year for their measure of life expectancy at birth, but none of us reading this now are lucky enough to be that fresh to the picture. Bigger gains than this modest trend, a trend that will see us dead with only a couple of additional years to show for it if it continues as-is, will require a radical shift in the research community's strategic vision, and a focus on repair-based biotechnologies. Not surtuins, in other words, and nothing that looks much like sirtuin research either.


I completely agree. This is a dead end. It's not cost-effective at all. When it comes to longevity genes, scientists should look at supercentenarians. I think it'll be easier to find genes responsible for longevity by examining supercentenarians' genomes than our metabolism. What is more, in this case we can expect 20 to 30-year gains in lifespan. This is something that is actually worth pursuing.

Posted by: Nick at September 22nd, 2011 12:26 PM
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