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Monday, March 12th 2007

The Ultimate Ambition

It has topped even the quest for lead to gold. The drive for immortality is almost as old as recorded history. It haunts myths and the efforts of the learned.

It isn’t merely a wild dream of the alchemists of the past, either. Today the drive to stop cellular senescence, and thus hopefully increase the life span of us exponentially, is the ultimate goal of the Transhumanism movement.

This Man Looks Like A Traveling Elixir Salesman…
…His Name Is Aubrey de Grey

Apoptosis (cellular death) is complex. From stopping telomerases from disappearing to inhibitor proteins science is looking around at how cells (and thus organisms) age and die.

No matter how they’re folding themselves under the umbrella of legitimate science, the history of those who have sought eternal life is one of gazing towards the horizon. When one thing doesn’t pan out there’s always the next big hope. The question is what is the next “big thing” in the quest for immortality?

As many have heard it may be Reservatol.

Resveratrol is the ingredient in red wine that made headlines in November when scientists demonstrated that it kept overfed mice from gaining weight, turned them into the equivalent of Olympic marathoners, and seemed to slow down their aging process. Few medical discoveries have generated so much instant buzz – even Jay Leno riffed about it in his opening monologue.

may work through sirtuin enzymes. Specifically the SIRT1 sirtuin in humans. From the Forbes article,

[I]t may be that just one of resveratrol’s many targets is the really magical one – a kind of master switch that turns on CR-like effects all by itself. Sinclair is in the latter camp: he believes that an enzyme called siRT1 is resveratrol’s key target, and that the compound works its magic mainly by activating that enzyme. (siRT1 is a member of the sirtuin class of enzymes, hence the company name.)

Reservatol’s sirtuin activation may be intimately tied to cholesterol restriction (Wikipedia: Cholesterol Restriction),

The hubbub about resveratrol began with a 2003 study by Sinclair’s group suggesting that the compound can mimic the effects of CR in yeast cells, boosting their life spans by 70 percent. The following year he and colleagues went on to demonstrate that resveratrol slows aging in roundworms and fruit flies. That made it the first compound to show anti-aging effects in widely divergent species. Then, last spring, scientists in Pisa, Italy, showed that its magic extends beyond creepy-crawlies: Large doses of the compound boosted life span more than 50 percent in a species of short-lived fish.

Is This The Key To Looong Life?

There are major questions about reservatol and sirtuins. Indeed, even about the role sirtuins play in life expectancy. The big news about sirtuins involved the Sir2 gene in yeasts. The big “breakthrough” was that increasing this sirtuin increased the lifespan of yeasts significantly. However, as David Lowe points out by linking to this article in the journal Cell,

But what if you measure lifespan by the amount of time the cells can live when they’re not dividing? That’s the subject of a new paper in Cell from Valter Longo’s group at USC, which they have given the provocative title “Sir2 Blocks Extreme Life-Span Extension.” Yep, deleting it actually extends the non-dividing lifespan of the yeast, and combining that with caloric restriction increases it even more. These yeast cells have some problems, though, some of which can be ameliorated by further mutations in the IGF-1 pathway (itself heavily implicated in metabolic rate and lifespan). Yeast with combined Sir2 and IGF mutations, under caloric restriction, live longer by up to sixfold, a startling increase.

The gist is this: increasing the sirtuin level (the method by which reservatol may work) increases the number of times a yeast cell line can divide/replicate, however it apparently decreases the temporal life of each individual cell. Indeed, deleting or decreasing the Sir2 level actually increases the temporal life of each individual yeast.


The point is this, despite all the smart people working on making it possible for you to live forever, the hype, for now, is just that. Who knows though, perhaps I’ll be looking back on this post in 200 years with a wink and a smile.

[Substrate Specific Activation of Sirtuins by Reservatol]
[Mechanism of Human SIRT1 Activation by Reservatol]