New Sirtuin Hypothesis by David Sinclair Group

Seeking to unblock the mysteries of whether sirtuins (more specifically SIRT1) actually hold the secrets to aging, a group of scientist lead by David Sinclair of Sirtris Pharmacueticals (now part of GlaxoSmithKline ) has put forward the latest hypothesis on the mechanisms of SIRT1's role within a cell. For those not well versed in molecular biology, the hypothesis is rather complicated. Sirtuin Investor will attempt to simplify it into layman's terms:

1. Each cell has a double strand of DNA that, if stretched out, would extend over six feet long.
2. Each of these DNA strands has about 20,000 genes or so.
3. Under normal operations, each cell must provide instantaneous access to a very limited number of genes depending on the cell type (i.e. blood, pancreatic, renal, bone marrow, etc.)
4. The primary role of the SIRT1 is to help a cell SUPPRESS all the genes it shouldn't be accessing.
5. SIRT1 also has an important secondary role...to act as the cell's handyman, moving into action to repair any breaks in DNA strands within the cell.
6. Unfortunately, when the SIRT1 puts on its handyman hat and moves into action to make DNA repairs within the cell, it temporarily vacates its chief role as gene suppressor. Remember, only a handful of specialized genes are supposed to be active within any given cell type.
7. With SIRT1 distracted from it's primary role, normally dormant genes can wake up start partying, in the process, playing havoc and causing damage to the cell (think of a bunch of teenagers at house party when naive parents go on vacation). In the best case scenario, this cumulative damage is what we see in ourselves as normal aging.
8. Find a way to over express SIRT1 (analogous to finding surrogate parents while the real ones are on vacation) and there are less opportunities for cell damage....and the aging process is slowed down.

Whether this hypothesis gains wide support is open to debate. However, the hypothesis is tantalizingly seductive. Only time will tell whether the idea of a fountain of youth is a reachable goal or still a distant fantasy.

One final thought: you think the social security system (and our entire financial system) is in trouble now, just think about what will happen if we achieve the ability to extend our lifetimes by 20%? Oy Vey! Keep taking that resveratrol!

New Sirtris Study Results Reported

Sirtris Pharmacueticals recently released the results of a new study on mice that, it claims, further validates Sirt1 as a target for the treatment of metabolic disorders and endurance enhancement, an excerpt of which follows:

"The NAD+-dependent deacetylase SIRT1 controls metabolic processes in response to low nutrient availability. We report the metabolic phenotype of mice treated with SRT1720, a specific and potent synthetic activator of SIRT1 that is devoid of direct action on AMPK. SRT1720 administration robustly enhances endurance running performance and strongly protects from diet-induced obesity and insulin resistance by enhancing oxidative metabolism in skeletal muscle, liver, and brown adipose tissue. These metabolic effects of SRT1720 are mediated by the induction of a genetic network controlling fatty acid oxidation through a multifaceted mechanism that involves the direct deacetylation of PGC-1α, FOXO1, and p53 and the indirect stimulation of AMPK signaling through a global metabolic adaptation mimicking low energy levels. Combined with our previous work on resveratrol, the current study further validates SIRT1 as a target for the treatment of metabolic disorders and characterizes the mechanisms underlying the therapeutic potential of SIRT1 activation."

With evidence that SRT1720 "robustly enhances endurance running performance and protects from diet induced obesity" it would not be a leap of faith to hypothesize that the professional sports world is already ahead of the pack in trying resveratrol supplements to improve athletic performance. After all, resveratrol does not have the issues of being a banned substance.

The entire study is available for purchase here.

Obama Victory Bodes Well for Verenium

One of the stark policy differences between John McCain and Barak Obama was their respective differences on ethanol. Obama favors ethanol subsidies, McCain opposes them. McCain essentially gave up on Iowa, the largest corn producing state in the nation with this position. If the consideration is solely corn based ethanol, there is justification for McCain's position. Corn based ethanol provides very little net energy gain, if any, over the underlying fossil fuels that go into the process of making it and has had the unintended effect of raising food prices. However, the fallacy of McCain's policy is that it fails to consider the next generation of ethanol technology called cellulosic ethanol. President Obama understands that cellulosic ethanol is the end game due to clear advantages over corn based ethanol:

1. Use of non-food crops
2. Use of relatively low-cost feedstock
3. Use of marginal lands for feedstock growth
4. A very beneficial net energy balance
5. Use of less fertilizer and water.

With the victory of Barak Obama, Verenium is now firmly seated in driver's seat of this emerging revolution in biofuels. Verenium's landmark agreement with British Petroleum has positioned VRNM to be one of the top performers over the next 12-24 months in the opinion of the SI Blog.

To learn more about Verenium and its potential, visit these SI blog entries:

Focus on Verenium and Cellulosic Ethanol
Forbes Article Highlights Accelerating Race for Cellulosic Ethanol Production
Interview With Verenium's John Howe

Do your own due diligence.

Resveratrol and Weight Loss - Personal Experience

As many readers of this blog have learned, the benefits of resveratrol seem to be numerous. Just read down the entries of the SI blog and you will find many blog entries highlighting the numerous potential health benefits of resveratrol.

My own personal experience seems to confirm one benefit: weight loss. I've been using resveratrol for over a year and a half. During that time frame, my weight has slowly declined from 193lbs t0 183lbs. I'm 6 feet tall and my goal is 180lbs. I don't believe my calorie intake has lessened and I my activity levelhasn't changed. Research has shown resveratrol's effect on fat cells. My personal experience seems to confirm this. Additional comments from other personal experiences are encouraged.

With that, I have started a new poll. Has resveratrol helped you lose weight?

OFF TOPIC: Two New Polls

Given the historic events over the last few weeks the Sirtuin Investor is conducting 2 new polls:

1) Should some form of the plan to approve the purchase of up to $700,000,000,000 (that's a lot of zeros) in mortgage backed securities be approved in order to help save the economy?

2)How will you vote for president?

Vote now.

Resceratrol: Now its Radiation Protection?

In a seemingly endless string of research into the potential health benefits of resveratrol, new research from researchers at the University of Pittsburgh shows that resveratrol, when altered with acetyl, protected cells from radiation in mouse models. The study was led by Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at the University of Pittsburgh School of Medicine.

This new research adds to resveratrol's reputation as a compond with an expanding universe of health benefits. In other unrelated research resveratrol has already been shown to have potential in many diseases of the aging.

Interview With Verenium's John Howe

Click here to watch a very relevant interview with John Howe of Verenium Corp.

Obama Versus McCain on Cellulosic Ethanol

Verenium investors should be aware of the materially different positions on cellulosic ethanol held by the two presidential candidates:



OBAMA's website..straight forward policy on ethanol:

• Develop the Next Generation of Biofuels: Barack Obama will work to ensure that advanced biofuels, including cellulosic ethanol, are developed and incorporated into our national supply as soon as possible. Obama will invest federal resources, including tax incentives, cash prizes and government contracts into developing the most promising technologies with the goal of getting the first two billion gallons of cellulosic ethanol into the system by 2013.

McCain's own word....against subsidies for ethanol

Verenium enters Landmark Agreement with BP

Like most small caps, the stock price of Verenium Corporation (profiled here on May 21, 2008) has languished with the stock market since the SI Blog expanded coverage to cover promising companies outside the sirtuin space with the elimination of Sirtris Pharmacueticals as a public company. Today however, Verenium Corporation, followed in the steps of Sirtris by announcing a landmark agreement with an industry leader. In this case it was British Petroleum. Unlike Sirtris, however, Verenium management, which owns an astounding 54.67% of the company, decided that the upside was too promising to sell the entire company to BP. The deal calls for the establishment of a joint venture to commercialize celluslosic ethanol and it includes $90,000,000 of financing from BP over the next 18 months

One major catalyst for this agreement is certainly recently passed legislation that mandates 21 billion gallons of advanced biofuel production by 2022, of which 16 billion gallons must come from cellulosic ethanol. That's one hell of a mandate considering that the cellulosic ethanol industry doesn't really exist right now. Any company that can take advantage of this legislation will have a very lucrative business. More importantly, that company will help us move forward towards true energy independence. Cellulosic ethanol has five principal advantages over much criticized, and rightfully so, corn based ethanol:

1. it uses non-food crops
2. it uses relatively low-cost feedstock
3. it uses marginal lands for feedstock growth
4. it has a beneficial net energy balance
5. it uses less fertilizer and water.


Verenium is a leader in this field and is currently optimizing the nation’s first true demonstration-scale plant capable of producing ethanol from non-food cellulosic biomass sources.

Do your own due diligence and remember, if you visit this blog primarily as a resveratrol user....immortality is expensive.

New Poll on Resveratrol Usage

Back in February 2008, the SI blog ran a poll on resveratrol usage. The results were as follows:

• I don't take any --- 19%
• Up to 100 mg ----- 11%
• Up to 200 mg ----- 20%
• Up to 1,000 mg --- 26%
• Over 1,000 mg ---- 22%

Given the volume of research that has become available in the last 6 months, a new poll is now being taken to examine how usage has evolved. To participate see box at the right.

NY Times Article - More on Sirtirs, Sirtuins and Resveratrol

You'd think that Sinclair, Westphal and Sirtris Pharmacueticals would be less inclined to push the media/press envelope now that Sirtris is part of GlaxoSmithKline. Not true. See the latest feature article in the NY Times. One interesting excerpt: Glaxo is considering the marketing of SRT501 as ad over the counter resveratrol supplement. If you are looking to try resveratrol today be sure to vist SI Blog sponsors on this page.

New Study: Resveratrol Helps Prevent Breast Cancer

New research into the health benefits of resveratrol continue. The latest comes out of the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center. This new research published in the July 2008 edition of Cancer Prevention Research shows that resveratrol inhibits can cancer formation in Breast tissue. An excerpt from the study follows:

Resveratrol decreased estrogen metabolism and blocked formation of DNA adducts in cells treated with TCDD and/or estradiol. Resveratrol also suppressed TCDD and/or estradiol-induced cell transformation. Thus, resveratrol can prevent
breast cancer initiation by blocking multiple sites in the estrogen genotoxicity
pathway

The entire study can be read here.

The body of evidence continues and expands as to the positive effects of resveratrol on the human body. As with other recent research, this latest study shows that megadoses of resveratrol were not required to gain the anti-cancer benefits.

New Resveratrol Research Thows a Curveball

Just as many have become confident that the fountain of youth can be found in a daily dose of resveratrol, new research is clouding the issue. The latest research on mice comes from the National Institute of Aging and was the result of a collaborative effort between the laboratories of Rafael de Cabo, Ph.D., of the Laboratory of Experimental Gerontology at the NIA; David A. Sinclair, Ph.D., of the Glenn Laboratories for Molecular Biology of Aging at Harvard Medical School; and an international group of researchers. This research showed:

The Good:

• Improved heart health.
• Improved bone density.
• Improved motor skills and coordination.
• Significantly reduced incidence of cataracts.
• Improved quality of life.
• Increased lifespan for mice fed a high calorie diet.

However, resveratrol DID NOT extend the lifespans of mice fed a normal diet. For now at least, this research debunks the belief that high doses of resveratrol mimic the life extending benefits of a calorie restriction diet.

Meanwhile another study performed by a group lead by Valter Longo, a molecular geneticist at USC, found in laboratory tests that reducing the level of SirT1 activation in neurons decreased the cells sensitivity to oxidation when compared to normal SirT1 activation (for those unfamiliar with SirT1 and other sirtuins, they are the genes believed to be activated by both a calorie restriction diet and resveratrol). However eliminating the SirT1 gene completely, caused the mice to die young.

What this all means is certainly still open to debate, interpretation and motivation. Sirtuin Investor has pointed out previously seemingly conflicting results on whether activation or deactivation of sirtuins is preventative to various types of cancer (see blog entry dated April 30, 2008.) It is advisable to read through all the research and and to look behind the catch phrases put out by the often superficial media. As the sirtuin research picture becomes less focused, shareholders of Sirtris Pharamcueticals who were dismayed by the cash tender offer by Glaxo may now be feeling a little more placated with the $22.50 per share in their pockets! Stay tuned.

Elixir Licenses Boston University SIRT1 Modulators

Trying to stay in the game of Sirtuin based drug development, Elixir Pharmaceuticals has signed an exclusive licensing agreement with Boston University to key intellectual property covering discoveries regarding the use of modulators of SIRT1.

Expert from Elixir press release:

"Modulation of SIRT enzymes has attracted considerable attention because of
their potential to address a broad range of diseases," stated Dr. Peter
DiStefano, Elixir's Chief Scientific Officer. "Based on nearly a decade’s-worth
of research, Elixir has amassed a broad intellectual property estate, which
includes compounds that activate SIRT1 and compounds that inhibit SIRT1. It is
an exciting time to be working in SIRT development and we are pleased to have
added this intellectual property from Dr. Stephen Farmer’s lab at Boston
University to our portfolio."

In January 2008, Elixir was forced to postpone its IPO due to unfavorable market conditions.

Resveratrol: Fat Buster?

In a study by Martin Wabitsch, a pediatric endocrinologist at the University of Ulm in Germany, evidence was presented that furthers the belief that resveratrol may act as a catalyst to reduce the body's production of fat cells. This latest study was performed on human cells in a laboratory test and showed how resveratrol inhibits the number of nascent fat cells that grow into mature fat cells. If fats and carbohydrates from food cannot be transformed into fat cells, they are typically broken down and burned as energy instead. If these lab tests are an accurate indication of the actual process that takes place in the human body, it would limit the addition of fatty tissue. You know, that little (or big) spare tire you carry around your waist that you can't get rid of? This research advances evidence that explains the notion of the "French Paradox". Although the French diet tends to be high in fatty food, the overall population has a much lower obesity rate than other developed countries. Many have hypothesized that high French consumption of red wine is offsetting the high fat content. Only in the last few years has resveratrol been identified as the actual molecule in red wine that makes this happen.

For more detailed coverage of this study refer to these articles in Science News and CBS News.

Evolving Resveratrol/Sirtuin Research

As many followers of the SI Blog may recall, I have often questioned seemingly contradictory research with regard to resveratrol and sirtuins. Resveratrol clearly seems to have promising health benefits, but questions of how it works are still being answered. For recent examples, review the entries on June 4, 2008 and the strikingly differing views between Sirtis Pharmaceuticals and Elixir Pharmaceuticals as it relates to sirtuins and cancer, posted on April 8, 2008. Since it is clear that research on the mechanisms on how this all works in the body is still evolving, it never seemed prudent to follow those who choose to mega dose resveratrol (over 1 gram daily) even though they have reported only minor short term side effects, if any.

The current state of evolving research on sirtuins and resveratrol is well detailed and referenced in the following article written by Bill Sardi. As Mr Sardi is the president of a resveratrol manufacturer, I want to make it clear that I do not endorse or offer any opinion on his product versus other resveratrol products. However, I believe his article is worth reading:


The science surrounding the sirtuin family of genes that control the rate of aging is changing so fast that it begs for a scientific update. Many health and longevity seekers are drinking a bit more red wine or taking resveratrol pills in hopes of prolonging their number of healthy years. Are they doing the right thing? Well, yes, it certainly appears so. But now there is greater understanding how small molecules found in nature actually produce longevity.

The discovery that a molecule commonly found in red wine, resveratrol, activates the Sirtuin 1 DNA-repair “survival” gene, a gene that is also activated by calorie restricted diets [Science. 2000 Sep 22; 289(5487):2126-8] brought immediate hope that a molecular shortcut could be utilized rather than having to deprive oneself of food to achieve healthy longevity.

Various small molecules were tested and it was found that resveratrol activates Sirtuin 1 to a greater extent than other small molecules like quercetin, fisetin, etc. Yeast cells lived far longer when given resveratrol. [Nature 425: 191-96, 2003] Then follow-up studies showed that resveratrol extended the life of fruit flies and roundworms. [Nature 430: 686-69, 2004]

And the resveratrol story only kept getting better. Researchers in Italy showed resveratrol prolonged the life of a cold-water fish. [Experimental Gerontology 2007 Jan-Feb; 42(1-2):81-9] And there was even more excitement among biologists when resveratrol prolonged the life of a warm-blooded mammal (lab mouse) and overcame the effects of a high-fat diet. [Nature. 2006 Nov 16; 444(7117):337-42]

The race was on to develop synthetic resveratrol-like molecules that can activate the Sirtuin 1 gene to an even greater extent than resveratrol by itself. Synthetically made Sirtuin 1 gene activators which could stimulate the Sirtuin 1 gene 1000-fold were unveiled. [Aging Cell 6: 35-43, 2006]

But now the picture isn’t so clear about greater and greater Sirtuin 1 gene activation, and more genes than just Sirtuin 1 may be involved here, and there is even (a) question as to the mechanism that produces in greater amounts of Sirtuin 1 gene-derived proteins.

In an animal study, modest increases of Sirtuin 1 gene protein improved cardiac health, while greater than a 7.5 fold increase in Sirtuin 1 gene protein induced heart failure in laboratory mice. [Circulation Research 100: 1512-21, 2007] This is certainly a red flag. Over-stimulation of Sirtuin1 needs greater scientific scrutiny before mega-sirtuin activator drugs are employed.

Within a year of the report showing resveratrol molecularly mimics a calorie restricted diet, researchers at the National Institutes of Health were reporting that food deprivation activates the Sirtuin 1 gene via another gene called FOXO3a. Elimination of the FOXO3a gene in animals inhibits the starvation-increased expression of Sirtuin 1 gene proteins. Furthermore, when the p53 tumor suppressor gene is eliminated, the Sirtuin 1 gene proteins are not upregulated. Thus resveratrol is now forced to share the limelight with the FOXO3a gene and the p53 gene. Biologists now claim in mammals, p53, Foxo3a and Sirtuin 1 all constitute a nutrient-sensing pathway. [Science 2004 Dec 17; 306 (5704):2105-8] That is to say, during periods of food deprivation, a number of genes are activated in defense of the organism.

Longevity seekers will be hearing more about the family of FOXO family of genes. The Sirtuin1 activator resveratrol works in tandem with the FOXO1 gene, whose proteins are translocated to the nucleus of living cells where they decrease the generation of free radicals and inflammation. So resveratrol is effective in this regard through the action of FOXO1 gene derived proteins. [American Journal Physiology Endocrinology Metabolism 2007 Jul;293(1):E159-64]

Biologists now recognize that one of the adverse effects of high insulin levels and high insulin-growth factor signaling is suppression of the FOXO gene family. Aging is accelerated by the suppression of the FOXO gene family, which results in generation of damaging free radicals. Here is how biologists explain it:

Biologists say “an understanding of the processes controlled by these FOXOs
should permit development of novel classes of agents that will more directly
counteract or prevent the damage associated with diverse life-threatening
conditions, and so foster a life of good health to a ripe old age. Just like caloric restriction, lifespan can be increased in various species by plant-derived polyphenols, such as resveratrol, via activation of sirtuins in cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO and other pathways to achieve their beneficial effects on health and lifespan. Current progress bodes well for an ever-increasing length of healthy life for those who adapt emerging knowledge personally (so-called 'longevitarians')”. [Journal Hypertension 2005; 23: 1285-309]

Even more perplexing, however, is a Harvard study showing that inhibition of Sirtuin 1 gene activity results in a decrease rather than an increase in senescence. Harvard researchers suggest that inhibitors for Sirtuin1 may have anticancer potential. [Oncogene 25: 176-85, 2006] How so? Most lay persons following this story were led to believe the Sirtuin 1 gene needs to be up-regulated rather than down-regulated to produce longevity.

Now researchers at MIT and Harvard show that a calorie-restricted diet does not uniformly activate the Sirtuin 1 gene in all organs of the body. In the liver, a high-calorie diet activates Sirtuin 1 and a low-calorie diet inhibits Sirtuin 1, which runs contrary to what was anticipated.

The researchers themselves explain it this way:

In summary, we show that the regulation of SIRTUIN1 by the diet is more
complicated than originally imagined. While it has been assumed that SIRTUIN1
activity increases generally during calorie restriction, we show that in the
liver the activity of this gene actually decreases. The regulation of SIRTUIN1
activity during calorie restriction is not only tissue-specific, but even
region-specific in non-homogeneous tissues, such as the brain. [Genes &
Development, published online June 11, 2008]

Do any of these revelations take the luster off of resveratrol? Hardly. But certainly the explanation of how resveratrol works is itself a work in progress. And while there may be momentary concern that resveratrol could in fact have the unwanted effect of inducing, or at least failing to prevent, the synthesis of fat and cholesterol in the liver, in fact, resveratrol-fed mice placed on a high-fat diet do not develop fatty liver and actually exhibit improved liver physiology and metabolic function. [Nature 444: 337-42, 2006; Cell 127: 1109-22, 2006]

And for all the followers of this unfolding discovery concerning molecularly-induced longevity who were initially introduced to the Sirtuin1 gene and seek to activate it via red wine or resveratrol pills, there is yet another revelation. At least two of the family of seven sirtuin genes share the role of lifespan regulation via nutrient availability, Sirtuin1 and Sirtuin6.
Furthermore, these same researchers who report on the role of Sirtuin6 also report that food deprivation doesn’t increase Sirtuin1 gene activity, but rather stabilizes this gene-derived protein which results in more of this protein being available. In other words, a calorie-restricted diet doesn’t increase the activity of Sirtuin6, but rather helps preserve it once it is produced. Here is how the researchers describe it:

These findings raise the possibility that, in mammals, several sirtuins mediate
the beneficial effects of calorie restriction on life span in a combinatorial
manner. Hence, a systematic approach is required when studying the role of
sirtuins in aging and calorie restriction. Furthermore, we propose that in order
to develop small molecules which could mimic the ability of calorie restriction
to prolong healthy life-span, one should search for master regulators with the
ability to promote the activities of multiple sirtuins. [FEBS Letters, In Press,
Corrected Proof, Available online 9 June 2008]

Well, there you have it, Sirtuin1 has a brother, Sirtuin6, and they are sharing the scientific limelight now with other genes, including FOXO and the p53 gene, with likely more to come. Furthermore, the activation of Sirtuin1 is not uniform in all tissues and organs and that in vitro studies (in test tubes) which measure activation of the Sirtuin1 gene may not provide a complete nor accurate picture of what is actually going on inside a living organism.

It is this author’s opinion that there is too much reductionist thinking here. Genes do nothing in themselves, they react to biological stressors, such as excess food, food deprivation, radiation, heat, cold, etc. Genes can also be targeted by molecules in the diet, but apparently in not such a narrow way, but rather more broadly. Albeit, the very advantage these small natural molecules like resveratrol have is that they affect a broad array of genes. [Journal Nutritional Biochemistry 2005 Aug; 16(8):449-66]

The human genome consists of 30,000 genes. Upcoming global gene array studies will provide a broader picture of how dietary-derived molecules affect the genome. Cherry-picking a single gene to describe it as “the holy grail” of aging may have been a bit premature. How many genes does a calorie restricted diet significantly upregulate? Around 200.

The next round of scientific discoveries will soon compare the effect of a calorie restricted diet, a resveratrol-supplemented diet, and a diet where multiple small molecules have been employed.
These are challenging studies because calorie restriction induces hundreds (if not hundreds of thousands) of biological changes, making it difficult to identify those that are causal, say researchers. [Journal of Nutrition 2001; 131:918S-923S]

However, aging results in different gene expression patterns specific to each tissue in the body, and the good news is that most alterations produced by aging can be completely or partially prevented by caloric restriction in both heart and skeletal muscle. [Cardiovascular Research 66: 205-12, 2005] Therefore, calorie restriction mimics with small molecules are very promising.

The small molecules that exert the greatest effect over the genome in regard to aging will all be found to be mineral chelators or controllers. [Neurobiology Aging. 2008 Jul; 29(7):1052-9; FEBS Letters 2003 Sep 11; 551(1-3):58-62; Ageing Research Reviews 2003 Jan;2(1):25-37] The gradual accumulation of minerals in the body, once full childhood growth has been achieved, explains the progressive aging experienced by humans. Removal of these minerals (chelation) holds the promise of restoring a youthful state to aging cells, tissues and organs, with the prospect of a biologically unlimited lifespan. –Copyright Bill Sardi, June 21, 2008.

Forbes Article Highlights Accelerating Race for Cellulosic Ethanol Production

A June 12th article in Forbes Auto highlights what is becoming a desperate race to produce low cost cellulosic ethanol. As I've prevoiusly reported on this blog, it is clear how disastrous an effect corn based ethanol has had on food inflation without doing much, if anything, to wean us off fossil fuels. With the USDA now reporting falling 2008 corn production, a crisis is in corn based ethanol production is taking hold. The mad rush towards corn based ethanol production of a couple of years ago is likely to be followed by a new rush for cellulosic ethanol production. This race is already in full swing as at least a half a dozen start ups are plowing money into cellulosic ethanol research.

Mark my words:

"Wall Street ANALysts are missing the

boat on the cellulosic ethanol story!"

At some point in the near future this will change and the ANALysts are likely to hop on the bandwagon. Refer to my blog entry on Verenium Corp. for the Sirtuin Investor pure play pick in this arena. Wall Street hasn't caught on yet and thus the current $2.27 VRNM stock price may represent a very favorable entry point with a market cap of only $145 million. According to Yahoo, only two ANALysts currently have ratings on VRNM.

These are the personal views of the Sirtuin Investor and should not be relied upon for your investment decisions. Do not make any investing decisions without first doing your due diligence.

SI Editorial: The U.S. Energy Dilemma

ITS HERE. The ugly Day of Reckoning in U.S. Energy Policy has arrived and there is plenty of blame to go around. Decades of inaction by our government, endless roadblocks by environmental groups, little national interest in conservation and an auto industry with a short term agenda that focused solely on the big profits of BIG SUVs. All these factors have finally caught up with us. It was inevitable......just a matter of time. Pay day has arrived and it's both painful and ugly.

NOW WHAT??????

Unfortunately, there will be much pain before we can get out of this mess. It will take a national effort to make it happen. The stark reality is scary. Not only is our lack of an energy policy hurting our standard of living, even worse, we no longer control our own destiny!! How scary is it that other countries control whether or not we can heat our homes in the winter or drive our cars in the summer? The Sirtuin Investor proposes the following common sense solutions:

• Remove the Roadblocks to Nuclear Power. - it's not perfect but it is efficient, abundant and produces NO CO2. France generates 80% of its electrical power from nuclear energy!!


• Sell Oil and Gas Exploration Leases off the coast of the continental shelf - we have two coastlines that may hold billions of barrels of oil. However, they have been off limits to drilling due to environmental concerns. It is understandable and reasonable to be concerned for our environment. However, desperate times call for desperate measures. Look at what Brazil has accomplished. At this point ANWAR is a no brainer. Are working class people less important than caribou?


• Embrace Cellulosic Ethanol - don't be swayed by the fiasco of corn based ethanol as it was always intended to be a stepping stone. Once again another country had the vision that we, up until this point, failed to see. Brazil is energy independent. We can get there too with the big legislative push currently in place for cellulosic ethanol. To learn more click here. You may even make some money.


• Continue to Push For Renewable Energy - we are on the road to progress in this area. Wind, Solar, Municipal Waste, Geothermal, Hydro, Tidal Energy. These are the long term answers that will eventually make a difference. How could anybody argue with off shore wind turbines, for God's sake? But they do!!


• Conservation - with energy prices at current levels conversation is finally happening on its own inertia. Big SUV's are finally being shunned by consumers. However, legislation should be enacted to officially require significant improvements in auto gas mileage requirements, something that should have been accomplished decades ago.

Nothing stated above is earth shattering. But we are where we are due primarily to a failure of our government act. It is important to get congress to take action now. Those inclined to do so should click on the little e-mail link below to forward this editorial to their representative in congress. Also forward to friends, enemies and acquaintances.

New Study: Low Dose of Resveratrol Mimics Calorie Restriction Diet

In an interesting new study of resveratrol, researchers from the University of Wisconsin concluded that low doses of resveratrol mimicked the effects of a calorie restriction diet in mice. That is good news for those who have been reluctant to take mega doses of resveratrol but have chosen to take lower doses.

An abstract of the study follows:

Resveratrol in high doses has been shown to extend lifespan in some studies in invertebrates and to prevent early mortality in mice fed a high-fat diet. We fed mice from middle age (14-months) to old age (30-months) either a control diet, a low dose of resveratrol (4.9 mg kg−1 day−1), or a calorie restricted (CR) diet and examined genome-wide transcriptional profiles. We report a striking transcriptional overlap of CR and resveratrol in heart, skeletal muscle and brain. Both dietary interventions inhibit gene expression profiles associated with cardiac and skeletal muscle aging, and prevent age-related cardiac dysfunction. Dietary resveratrol also mimics the effects of CR in insulin mediated glucose uptake in muscle. Gene expression profiling suggests that both CR and resveratrol may retard some aspects of aging through alterations in chromatin structure and transcription. Resveratrol, at doses that can be readily achieved in humans, fulfills the definition of a dietary compound that mimics some aspects of CR.

A dose of 4.9 mg per kilogram of body weight was given to mice in a study reminiscent to the celebrated Harvard study in November 2006 by David Sinclair. The media attention that followed helped set the stage to orchestrate the IPO of Sirtris Pharmacueticals. From a resveratrol users perspective a 200lb. and 150lb. individual would take a daily dose of 445mg and a 334mg, respectively to mimic the doses in the study. Another interesting aspect was that the beneficial results were observed in "middle aged" mice as well as "old aged" mice. Surprisingly, the study concluded that Sirt1 levels were not over expressed as in previous studies although the health benefits were evident. To read the study in its entirety, click here.

To the Sirtuin Investor, a couple of questions: Will an even lower dose produce the same results? What are the implications of this study to the drug candidate NCE's of Sirtris Pharmacueticals that are 1,000 more times as potent as resveratrol?

Glaxo Sirtris Merger is now Final

The completion of the merger between GlaxoSmithKline PLC and Sirtris Pharmaceuticals was announced today with 97% of shareholder's tendering shares. This transaction puts an end to the only pure play sirtuin investment available to retail investors. Another Cambridge, Mass. based sirtuin focused company, Elixir Pharmacueticals, previously postponed its IPO due to poor equity markets in January 2008 and withdrew its IPO filing with the SEC last month. Don't be surprised if the IPO is revisited this year.

The Sirtuin Investor wishes Glaxo and Sirtris great success in pursuing the promise of sirtuins to treat diseases of the aging.