Tracing the Pathway Back for Resveratrol

Resveratrol in and of itself is likely not terribly interesting for work on longevity - and certainly not worthy of the hype surrounding it. The same probably goes for sirtuins in general. This, however, is still a good example of work on tracing back the pathways of action of a metabolic change agent: "Research has previously suggested that resveratrol acts through activation of the sirtuin (SIR) gene family. This gene pathway, though controversial, has been implicated in life extension across several species. It has been reported that SIR extends lifespan in much the same way as caloric restriction which itself in turn may activate SIR. It has remained unclear however if resevertrol directly activates SIR or if it acts on SIR indirectly via another intermediary biochemical pathway. The current study successfully answered that question. Using several cell biology techniques the authors were able to demonstrate that resveratrol actually functions to activate SIR indirectly. They showed that resveratrol is really a phosphodiesterase inhibitor (PDE4). They demonstrated that reducing PDE4 allows cyclic AMP (cAMP) levels in the cells to rise. cAMP then increases the activity of AMPK which next increases NAD+ which finally increases SIR. This elegant study then went on to prove that the same life extending benefits of resveratrol could be achieved in rats by administering them the PDE4 inhibitor rolipram. ... inhibiting PDE4 with rolipram reproduces all of the metabolic beneļ¬ts of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. "



This is a typical example of what is wrong with our liberties. We are allowed to drink battery acid but we are not allowed to buy rolipram. I can't understand why humans are not allowed to try non addicting substances on their own. Rolipram and Piclamilast (both selective PDE4 inhibitors) have never been made available to the public while both seem to have great therapeutic potential. Ridiculous.

Posted by: Singaporean at February 15th, 2012 9:08 AM

These other PDE4 inhibitors have much better bio-availability characteristics than reservatrol, so it should be easier to obtain whatever benefit there may be through them. I'm all for allowing people the freedom to do as they please with their own bodies, of course.

Posted by: Jose at February 16th, 2012 3:28 AM

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