For the past decade and a half at least a billion dollars in research marketing and publicity money was spent trying to find a home for a class of epigenetic molecules (histone deacetylases) known as sirtuins.
If this sentence has your finger hovering over the mouse, ready to move onto something more interesting and familiar, HANG ON! At least let me set up a little back ground for you.
A fellow by the name of Sinclair became pretty famous for his research into longevity by researching a molecule initially found in red wine grapes. That molecule was known as Resveratrol. Subsequently, after a lot of typical internet finagling, the molecule became known as a fountain of youth, a telomerase activator, a telomerase inhibitor and all kinds of other confusing and wonderful things that led to at least a few hundred million dollars for various vitamin gurus and vitamin companies.
And for a long time, the claim was made that Resveratrol modified the all-important class of molecules, known as sirtuins. It was supposed to be a “sirtuin activator”. More than one famous guru and a lot of famous supplement companies and vitamin foundations touted this as a fountain of youth.
Even the good Dr Oz got into the act, although no one is 100% sure if it was willing participation, or not. Dr Sinclair did OK, too. He sold Sirtris Pharmaceuticals to Big Pharma giant GLaxo Smith Kline (GSK) for $750 million, one of the biggest dollar amounts for a small bio medical firm ever paid. Soon after, some of the Sirtris execs raised some eyebrows when they (now working for GSK) started selling Resveratrol online.
Sadly for Resveratrol fans, GSK had to halt the trials on the “super” Resveratrol, developed by Sirtris, because of human toxicity and lack of efficacy. In addition, most of the findings associated with Resveratrol could not be replicated. OOOPS! There goes 750 million.
If you’ve ever wondered why Big Pharma has been so slow to jump on the anti-aging bandwagon and develop the magic pill they so desperately want, this is no small part of the reason. It parallels the multi-billion dollar failures, fraught with lawsuits and human harm that have occurred as a result of Big Pharma’s failures to develop effective weight loss drugs.
Damn! The basics of human behavior and human existence are so friggin’ complicated!
Hint: now that we are beginning to piece together the epigenome and the role of epigenetics in all cellular functions, the day is coming when both magic pills will become available. Heck, we already have TA-65!
Historically, the link between research and eventual true human longevity will go straight through TA-65. Not so, with Resveratrol.
Now, all is not lost for Resveratrol. It turns out it’s a good antioxidant and a modifier of some important molecules, known as “adipokines”, which help the body manage energy, glucose, fat and stress – all important stuff. This cannot help but influence telomere health, at least indirectly. But as I proved to myself and at least a few people who would listen (along with some help from super scientist Bill Andrews of Sierra Sciences), Resveratrol is neither telomerase activator nor inhibitor.
OK, now let’s back up to the molecules that started all this – sirtuins. I predicted a bunch of things, when I wrote my portion of The Immortality Edge and the many newsletters that have followed since then. One of them was that calorie restriction would be a totally impractical way to extend life, and the other was that telomeres and sirtuins would be linked. I said that I thought telomeres would eventually be shown to influence the activity and expression of sirtuins.
While that last thing has not yet come true, its corollary has. Sirtuins have begun to be shown to influence telomere length.
There are seven or eight specific sirtuins for humans that we know of. So it’s time for another prediction!
I predict the sirtuins will turn out to be like the Chakras – an energy centered concept that features in tantric and yogic traditions of Hinduism and Buddhism.
We started out hearing about seven or eight and now there are at least 21! I am willing to predict we’ll wind up with at least 21 sirtuins, when it’s all said and done, and no, I am not implying the two concepts are linked. Or am I!?
Anyway, the most studied sirtuin is SIR 1. Most studies have shown that this protein only confers stress resistance and improved health in the face of stress itself. Then again, who among you eats perfectly, sleeps perfectly and lives a stress-free life! We don’t even know what those things mean for most people. Again, as epigenetics evolves and allows the study of individual metabolomics (how each of us processes everything!), we will have an answer and it is not likely to be the same for all of us by a long shot!!! But the sirtuins will be a big part of it and of course, so will your telomeres!
The problem with the sirtuins as longevity molecules is that up until now, SIR 1 the most studied of them, did not confer longevity. SIR6 however, may in humans. Notice I said “up until now”. A recent study (see below) suggests that there are genetic variants, that do indeed make a population of people stand out for their longevity. Now the study has some shaky/shady assumptions and statistical play. But it is still intriguing and needs further study, of course.
I would like to suggest, to the authors, that they reverse the direction of their study and see what role telomere length has on the expression of the sirtuins, specifically SIR1 and 6. Then I think we will really get somewhere.
It won’t get GSK their $750 million back, nor will it restore Resveratrol to its (funnily continued!) much vaunted status as a longevity drug. But it will get us closer, in a meaningful way, to solving what I think is the disease called aging.
In my next life, I want to come back as a basic science researcher. Then again, if I live long enough, I could go back and swap my MD for a PhD and have a ball.
Anything is possible, so don’t give up – and take your fish oil, TA-65 and if you must, your Resveratrol.
Biogerontology. 2012 Apr;13(2):119-31. Epub 2011 Oct 5.
Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity.
Kim S, Bi X, Czarny-Ratajczak M, Dai J, Welsh DA, Myers L, Welsch MA, Cherry KE, Arnold J, Poon LW, Jazwinski SM.