Can we hack the opiate system?

Commented on October 09, 2011
Created October 07, 2011 at 5:57 PM


"It is well known that if you put C. elegans on a restricted diet, you can extend its lifespan by 40 to 50 percent," Gill said. "However, we were amazed to see that if you add back just one of these NAE molecules, eicosapentaenoyl ethanolamide, it completely abrogates the lifespan extension." Importantly, this particular NAE is similar to endocannabinoids in mammals, which regulate many different physiological processes including nutrient intake and energy balance, as well as inflammation and neuronal function. "The identification of other components of a novel endocannabinoid system in the worm now brings a new model system to the many researchers studying NAE and endocannabinoid physiology," said Gill. Intriguingly, the study also established a link among fat, NAE levels, and longevity. Other studies in rodents have shown that the availability of fatty acids can influence NAE levels. However, Gill and his colleagues found that in a genetically altered strain of C. elegans the inability to produce certain polyunsaturated fatty acids was not only associated with a reduction in levels of specific NAEs but also with lifespan extension. He added that the study's findings could shape future drug development efforts to influence aging and age-related disease."


What I would suggest is that you have certain effects only when you target a specific receptor, that is somewhat hard to replicate in real life. In real life, you would influence more than one receptor at a time which might alter these effects, by dietary means. Coenzyme alpha lipoic acid? If so, where is the evidence that it helps to reduce methionine levels?

Some would say just restrict methionine and do not bother with a substance that helps to reduce it. So maybe using lipoic acid to keep methionine levels down a bit. Methionine Sulfoxide Reductase, which appears in two forms, one that can deal with left handed and right-handed oxidised methionine. The enzyme can be boosted by food substances. Probably, methionine restriction and boosting Methionine Sulfoxide Reductases (and similar enzymes like thioredoxin, and Lipoic Acid, would have a very substantial health prologing effect. the principle endocannabinoid stimulants are from Omega 6 fatty acids.

The effect of increasing O3 is to reduce the availability of these substances. However, O3 fatty acids can degrade into CB agonists of their own.

Net effect? One has to consider that O3 and certain other substances can increase net fatty acid oxidation, which is probably very important, because it probably means less substances are available for hitting CB receptors - I'm thinking of PPAR agonists and carnitine in this instance.

But this line of inquiry also throws up the unexpected finding of synnergy between PPAR Alpha and CB receptor agonists on reducing pain.

I'm thinking here that excess CB receptor agonism reflects inefficient oxidation and shuttling of aldehydes into mitochondria, or excess ROS in the cell, therefore acts as an important pleotrophic signal that reflects cell stress. Why it signals in a way that influences life span, I can only conclude is because I think that O6 fatty acids more than O3 fatty acids are essentially over stimulating this receptor. This may be a means by which excess O6 seems to be harmfull. The PPAR's I think are involved here (or rather, the lack of which).

Thinking on these lines also has suggested to me a mechanism for how Methionine causes reduced lifespan, it reacts with radicals in proteins preferentially and readily oxidises and switches from one enantiomer to another, which disrupts protein function. This is sacrificial but only beneficial as long as you can correct it, which in fact is determined by an important antioxidant enzyme in both left and right handed forms which specifically corrects this amino acid, which is turning out to have some important roles in health according to recent literature.



on October 09, 2011
at 04:48 PM


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