Thursday, November 27, 2008

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!

Wednesday, November 19, 2008

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.

Wednesday, November 5, 2008

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.