Whole body hacks ?

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An example of how it is hard to hack a hacked system follows.

Previously I mentioned a quote from Francis Crick (1962 Nobel prize winner for the co-discovery of the structure of DNA (1953)) that biology is a hacked together system rather than engineered from the ground up. This general idea makes sense at an evolutionary level – one tweak, or system, was hay-wired on top of the next for whatever evolutionary gain. Hence, the system is a hacked, ad-hoc assembly that works very well for its appropriate environment, but not easy to reverse engineer.

The great hope of health science is through the intervention of a drug (usually acting by a single mechanism) to alter the biological system to cure, or treat, various diseases. Now it is an open question with all the redundancy and irregular and/or overlapping systems how effective this paradigm can be.

For example purpose, one biological problem that is getting an increasing level of interest is in the general health field of improving the overall health of humans, which can lead to increased longevity or just an increase of health in aged humans – instead of a life with chronic illness and constant health challenges.

Calorie restriction (CR) in its various forms has proven to improve the health and extend the lifespan of numerous organisms. However, many people correctly argue that is unreasonable to expect a significant percentage of the human population to adopt such ‘will power’ driven diets (just have to look at the obesity epidemic to see the logic of this argument). Therefore, there is a large search for calorie restriction mimetics (CRM) to produce the same effects. So like other health scientists, these scientist are looking for a pill to treat the masses, and in this particular case they want to produce the same effect as CR.

Resveratrol (found in wine) is the great hope, which I have covered previously . The main proposed mechanism of resveratrol is to increase the protein Sirt1, (sirt1 is one member of the sirtuin family of proteins) which is reported to be increased with CR in many tissues. Ouborous has a couple of very good posts on resveratrol and sirtuins .

David Sinclair – one of the two big guns in the resveratrol/sirtuin field who co-founded Sirtris Pharmaceuticals, made big news recently when the company was bought by GlaxoSmithKline for 720 million dollars (meaning a stock price of $ 22.50, which is a nice tidy sum over the closing price of $ 12.23 – as of April 23, 2008 – just before the deal). What David Sinclair and company has developed (and GlaxoSmithKline bought, bet on) are potent inducers of Sirt proteins (potential calorie restriction mimetic). David believes when his drug hits the market in 4 or 5 years for diabetes that his pills will only cost 3 or 4 dollars each, and once it comes off-patent only pennies. Alright – a cheap calorie restriction mimietic is coming down the pipeline.

Now what is interesting is a new Sirt1 paper by the other big leader in the field of resveratrol/sirtuin and longevity, Guarente (former supervisor of Sinclair) was recently published. Normally it is thought that CR increases Sirt1 expression (at least protein level and activity, not necessarily at the mRNA level) and this is what Guarente’s group found in the muscle and fat tissue of CR animals. However, in the liver they found lower levels of Sirt1 compared to the control fed group. Therefore, a pill that systemically increases sirtuin levels in all tissues might not produce the same effects as CR – and could even potentially produce some opposite effects of CR. High calorie diets in this study increased Sirt1 levels in the liver. The final line in the abstract is: “Our findings suggest that designing CR mimetics that target Sirt1 to provide uniform systemic benefits may be more complex than currently imagined.”

I think this statement is a caution to the biological field in general and obviously the Sirt1/Resveratrol field specifically.

This example might point out why when you want to hack a hacked system that you need to worry about the devils in the details, and why relatively simple (CR), but highly effective global results (increased lifespan, etc) might not be so easily addressed by a single magic bullet.

I don’t want to sound like a broken record (and I will get off this topic tomorrow), but like yesterday you can wait 4 or 5 years for a pill to produce overall health benefits (that may not work as well as we expect – see above), or do something today to improve your health. None of us are getting any younger, as I understand how time works. Go and try something novel today, go exercise, go light on your lunch today, go learn something new.


6 comments for “Whole body hacks ?

  1. Jpat
    June 18, 2008 at 1:33 am

    I have been under the impression that Rosalind Franklin was the researcher who was the actual discoverer and around the time of her early death, the two who got the credit acquired access to her research.

  2. Dr. James Resnick
    June 18, 2008 at 2:14 am

    According to the NIH formula for converting from mice to humans the correct dose based upon the published studies is between 400mg and 4,000mg for a 70 kg man. The consensus seems to be that around 1,000mg is appropriate for a preventative dose and twice that to treat an existing condition.

    Since the Dr. Sinclair study was published in Nature a flood of somewhat dubious companies have sprung up selling resveratrol. Most of the dodgy ones have some variation of resveratrol in their name and sell only one or two products. One even makes his capsules in a rented house in Florida.

    Consumer Lab, an independent testing authority, evaluated the major brands and found many lacking in content and quality. The ones that passed their evaluation were Biotivia, Transmax and Bioforte. A product by Life Extension Co. failed badly with only 26% of the claimed resveratrol. Another brand, Revatrol, had virtually no trans-resveratrol. The ConsumerLab test results are available on their web site.

  3. June 18, 2008 at 10:29 am

    I have researched resveratrol suppliments and I have found that Biotivia, Transmax and Bioforte is to be avoided. It has many impurities in it.

  4. Ward
    June 19, 2008 at 7:46 am

    JPat,

    you are correct Rosalind Franklin was instrumental in the discovery of the structure of DNA. There has been several books and articles discussing if she received appropriate recognition for her contribution. Many believe that she should have also been rewarded the Nobel prize along with Watson and Crick.

  5. Ward
    June 19, 2008 at 7:50 am

    Dr. James Resnick,

    you make some great points – thanks. I have read similar information regarding that many of the resveratrol sold out there does not measure up to what is advertised. But I do not know anything about the specific brands. But I presume the results form ConsumerLab test results are out there on the net?
    thanks

  6. Ward
    June 19, 2008 at 7:53 am

    Dr. Ben Ebstein,

    thanks for the comment. It appears that you have found at a personal level the opposite results of Dr Resnick. I have no specific information regarding which brand of resveratrol is good or bad. But my overall argument, as suggested from the paper I cited, is that resveratrol, or any molecule that raises Sirt1 systemically may not produce the same results as calorie restriction. And that the biology of sirt1 (sirtuin in general), resveratrol – is more complex than we would like it to be.