A Few Additional Sirtris Links

I thought I'd point out a couple of links of interest to those following the recent burst of news on resveratrol and the efforts of Sirtris Pharmaceuticals. First out of the gate, an interview with David Sinclair (co-founder of Sirtris) by Charlie Rose can be found at Google Video. From Sinclair's Harvard faculty page:

Our goal is to devise ways to prevent and treat the major diseases of society by manipulating genes that control how fast we age. ... These genes underlie the remarkable effects of the diet known as calorie restriction (CR), which delays aging in every species tested, from yeast to primates. CR is currently the only treatment that can prevent all diseases of aging including cancer, heart disease, osteoporosis, diabetes and neurodegeneration. Recent studies in our lab and others demonstrate that the ability of CR to extend lifespan in models organisms is governed by the Sirtuins. Animals lacking Sirtuin genes do not respond to CR and additional gene copies extend lifespan. Based on these findings, we have engineered small molecules that can activate mammalian Sirtuins in vivo, with a view to developing drugs that can (i) treat the diseases of aging and (ii) promote cell survival and recovery following an injury.

This is one of the most representative and advanced efforts of that segment of the research community presently attempting to safely change metabolism to slow aging. Unfortunately, given that the FDA will not approve any treatment for aging itself, these sorts of efforts are channeled into developing treatments for specific age-related conditions - the short-termist and ultimately ineffective process of patching up the consequences of aging, with no impetus to commercialize preventative methodologies. This is not good: you get things done by getting things done. If you're not working on A, you're not working on A, even if you're working on B that is related to A. Regulation in the US steers research investment and infrastructure away from making any serious effort to repair or prevent aging. This must change.

The present day mainstream approach to age-related degeneration, disease and frailty is a function and outgrowth of a historical lack of knowledge; if you don't know why the dam is crumbling, you get to plugging the holes and damn the expense. When plugging the holes is all you can do, then it's all you can do - it'll cost the moon and the dam will collapse only a little later than it would otherwise have done.

We can do better than this. Not right now, but soon.

But back to Sirtris and their present work:

Elixir and Sirtris:

So researchers are developing drugs to treat or prevent aging-related diseases like diabetes or obesity. The current explosion of anti-aging research dates to the 1930s when scientists discovered that dramatically reducing an animal's caloric intake will pile on extra years. ... Sirtris researchers have developed small molecules aimed at triggering the health-promoting effects from caloric restriction found in sirtuins, a class of enzymes. Elixir is also researching sirtuins, but it's seeking ways to treat diabetes and obesity by targeting ghrelin, a protein released in the stomach that regulates hunger and metabolic functions."

Press Release on Sitris' SRT501:

Sirtris Pharmaceuticals, the leading sirtuin therapeutics company, announced today that SRT501, its initial clinical candidate which is a proprietary formulation of resveratrol with improved bioavailability, has been administered to patients with Type 2 diabetes in a human Phase 1b clinical study. Sirtris is studying SRT501 as a drug candidate for Type 2 diabetes, based in part on the scientific evidence that sirtuin activation, by means of compounds like resveratrol, has been shown to have a positive effect on key clinical measures for diabetes.

Lastly, a teaser via Pimm and Chris Patil suggests there are more interesting attempts at metabolic manipulation to come:

I think the first really useful technological life extension will have a very familiar form, e.g., “take this pill and call me in fifty years when you’re still alive.” Drugs that activate sirtuins and related pathways are very promising (I can’t spill the beans but I saw some amazing data at Cold Spring Harbor suggesting that there are already several working drugs). Once we’re better able to get our brains around calorie restriction, I think that CR mimetics will be right behind the sirtuin-based drugs. To the extent that these sorts of drugs will help prevent acknowledged illnesses like Type II diabetes, there’s already a clinical indication for them, so they should sail through approval on that basis.

Like it or not, the main thrust of the research community interesting in healthy longevity is presently towards metabolic manipulation and slowing aging. If we want better ways forward - fixing age-related damage, rejuvenation and reversing aging - to gain greater funding and come to dominate, we're going to have to prove our case.

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I'd love to either get in a clinical trial or order resveratrol. I'm a candidate, believe me. Congtratulations on your research and development Dr. Sinclair and team!

Years ago, I thought of writing a book called "The Last of the Old People" as a sci fi story. I wish I had written it. It looks like you at Sirtis may make my thesis come true! Should I write someone to support you? Thanks Cathy

Posted by: Cathy Carver at November 25th, 2006 3:11 PM

I, and I am sure many, many people would love to get in your clinical trial for resveratrol. Short of being able to get into the trial, why does Sirtris not sell SRT501 as a non FDA approved "nutritional supplement" with all the necessary disclaimers? I understand there are other companies that sell tablets that they clain is resveratrol, but do they have the necessary quality control to create what you have used in your tests?

The truly conclusive test would take a single lifetime. Most of us are not willing to take that long.

Posted by: Mike Wong at December 15th, 2006 9:21 AM

If we have the means to invigorate a segment of the population that harbors an immense quantity of intellectual capital = wisdom - why not? Think of the benefits to the planet!! to the younger segment of the populaiton - people will not eat dirt at an earlier age and take this knowledge with them. I do not believe that this vein of thought requires debate. More benefits = less dollars to maintain an aging population,
+ productivity, less maintenance by progeny,higher GDP, increased competitiveness in a flat earth - need I say more???

Posted by: herdeka bacchus at February 11th, 2007 11:56 AM

I wish to know any research advances on Huntintong´s disease and how revestratol could help to reduce or improve the patient´s health.

Posted by: Juan F. Blanco at July 22nd, 2007 11:14 AM

Congratulation's on your research! Keep up the good work. Are there any investment opportunity's?
Thanks Dan Carlson

Posted by: Dan Carlson at July 24th, 2007 6:53 AM

The Boston Herald Sunday, September 2, 2007 did a big spread on Sirtris. Red Sox's John Henry has invested millions, I believe..Most interesting was the basis for the discovery of Resveratrol: a substance in red wine that mimics the actions of a restricted calorie diet: makes the cells work more effectively and increases health and longevity. Do I have it right? Sirtris is based upon this idea. A member of my family will be 91, is as thin as a famine victim, has no teeth, but spends much of his day trying to eat and get nutrition, and is hearty and enviably sharp- written in his chart: "this patient hasn't seen a doctor in over thirty years, possibly to his advantage." Can it be the restricted calorie diet that's working for him? Please let me hear from you. Sirtris is holding at @ $13.00 per share; symbol is SIRT

Posted by: Rebecca at September 3rd, 2007 2:28 PM

Count me in on any clinical trials for your resveratrol based product!

Posted by: Susan Collins at February 24th, 2008 5:27 AM

I also would love the chance to take part in any clinical trials for resveratrol.

Posted by: whitney at April 1st, 2008 7:34 PM

I would like more info on this subject, watching
Barbara Walters on abc talking about living to be
150 year old. I would love to support your scientific research, an will support any sirtis shares. My grandparents lived to be 99-101,could this be in our genes or dna? Please send any material to my e-mail. Congtra keep up the good

Posted by: Josephine Ortiz at April 1st, 2008 8:05 PM

Well it would appear that the resveratrol mimics the actions of a CR diet and the modifications of histones into the genetic evolution of the cells. Histones are fatty protein molecules that bind to the DNA and (among other things) essentially turn genes on/off by blocking their expression. If you block the expression of proteins that are necessary for normal life, you encounter disease common in older people. Interrupting this "normal" progression seems to be the key. If I were to make a wild guess, I would say that resveratrol controls the breakdown of these histones, gives them structural integrity and helps prevent the formation of telomeres.

I wish they had a lab close to where I live. I would love to return to the lab and “tinker” with my wild ideas.

Posted by: Tom at April 4th, 2008 7:35 AM

Live in Goodyear Az.

Am available for clinical trials.

Am aware and excited on your findings.

Am confused on numerous products available, I.E does Sirtris back Resmedin ? Go to Sirtris Web and up pops a variety of Resveratrol (some free ).

Posted by: Helen Hurley at April 24th, 2008 4:35 PM

I would really love to participate in your clinical trials. Please let me know when,as and where they might be held.

Posted by: Fred Zurofsky at January 25th, 2009 5:07 PM

I would also be interested in being involved in clinical trials.

How do the over the counter resvertrol suppliments compare to what Sirtris is using?

Posted by: Christina L at January 25th, 2009 5:07 PM

i am a 46 year old women who has been fighting breast cancer for 12 years I am now stage four with mets to bones only. I have been taking resveratol for the past six months but after viewing sixty minutes i'm a bit confused. Is Sirtris researching something different or just a higher dose than what is now available to the public? I would also be very interested in any clinical trials having to do with cancer and resvertrol.

Posted by: leanne podwoiski at January 25th, 2009 8:40 PM

would like to be included in resveratrol trials also

Posted by: helen bigelow at January 26th, 2009 4:55 PM

Recently diagnosed Type II diabetic and bilateral breast biopsies for 'calcifications'. Would resveratrol help halt or even reverse any of my conditions? Are there any Sirtris resveratrol products on the market now? Are the ones out there now any good? I also think I would be a good clinical trial candidate, depending upon the qualifications you are seeking. Otherwise at least a trial customer. I have read in the past how red wine lowers cholesterol, and there is even an old remedy 'Grape Cure' for cancer, which I have no stats on, but it is obvious that grapes and/or their skins have beneficial uses for health maintenance and/or cures. Count me in.

Posted by: luganrn at January 30th, 2009 9:08 AM

I am interested in clinical trial opportunities. I am a healthy 47 year old woman, but a severely stressful lifestyle has taken a serious toll on my physical appearance. A complete hysterectomy a year ago (with no hormone replacement)has now also affected my energy levels and is aging me even faster.......

Posted by: Kym Adamson at January 31st, 2009 7:46 AM

i also would like to be in a clinical rial- i think my husband and one of my grown children would also be appropriate for this

Posted by: sue cunningham at January 31st, 2009 6:21 PM

How do the benefits of red wine containing resveratrol interface with the recent caution given women that regular use of wine can cause breast cancer?

Posted by: Rosemary Everett at May 12th, 2009 10:19 PM

I have Ulcerative Colitis and presently take Resveratrol. I was confused about many of the available products and would like to try the one from you (the compination of resveratrol and whatever it is to make the bioavailability longer). Anyway, I have felt so much better after 6 months on Resveratrol and have had no episodes. I would be interested in a study too on UC.
Thank you and keep on with the research!

Posted by: Jutta Peters at September 24th, 2009 7:07 PM

have Ulcerative Colitis and presently take mesalazina and resveratrol.

I would be interested in a study too on UC.

Thank you and keep on with the research!

Posted by: jorge perez at September 3rd, 2010 8:27 AM
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