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Resetting Biological Pathways


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Hi,

This is from user Lawrence over on Longecity.

"Early in 2014 a group of 7 males, aged 45 to 66, decided that we would do a group buy of NMN. Our designated lead guinea pig is a molecular biologist and he began taking NMN late in 2014. 

In the beginning we monitored his blood work with monthly full panel blood tests performed by LabCorp. We believed that inflammation levels were a good indicator of health and aging, so we added two inflammation tests to the standard panel. The inflammation markers that we tracked were; C-Reactive Protein, (CRP), Tumor Necrosis Factor-Alpha (TNF-α) and Interleukin-6 (IL-6). As he began the NMN dosing (3,500 mgs of NMN twice per day) we noted a steady increase of inflammation peaking at week 4, followed by a significant decline to the lowest inflammation levels at month 2 and then a steady rise that stabilized by month 6 at a slight improvement to his baseline inflammation numbers.

We theorized as follows: During the 1st month the NMN had activated all of the Sirtuins and they had gotten busy with all of their long neglected biological “housekeeping” functions. The inflammation levels rose to get this accomplished. Once the Sirtuins had gotten everything in order, the inflammation levels dropped to their low point at the end of month 2. We attributed the slow and steady rise back to the baseline inflammation levels at month 6 to a homeostatic negative biological feedback loop kicking in.

While his inflammation level was rising, we researched the issue and came up with a theory as to why that was happening. Our theory was that the increase of activity by Sirtuins was out of balance with the other anti-aging pathways and the body was reacting by shutting down the Sirtuin activity brought on by the increased level of NMN. We theorized that by activating 2 other major anti-aging pathways (mTOR and AMPK) that we may activate all 3 of these anti-aging pathways in a balanced manner thereby achieving a sustained homeostasis. We added 2 compounds to our NMN and awaited the results.

We were very pleased with results and the other 6 members began taking NMN along with the 2 other compounds. All of our blood tests have showed the same dramatic and sustained decrease of inflammation. Since that time we have continued to research and experiment by adding and/or replacing compounds and adjusting their ratios to each other. In our current iteration we are using a 5 compound formulation to activate a total of 9 anti-aging pathways that sustains the NMN activation at its peak anti-inflammation levels."

This is the link to their patent application: https://patentimages.storage.googleapis ... 2311A1.pdf
A key takeaway from this is his use of "antioxidant defense activators". Scroll to page 91 of the patent application. He hasn't said what the 5 compound formulation to activate the 9 anti aging pathways are.  The patent mentions H2O2 as the antioxidant defense activator of choice. However my stomach cant handle hydrogen peroxide (even 3 drops in a large glass of water). Therefore I would like to follow up on the alternatives mentioned in the patent application.

I'm not a biologist nor am I studying biology so my knowledge of the subject is very limited. Therefore I would appreciate any help in associating this list of antioxidant defense activators with their appropriate anti-aging pathways. The list is as follows:

  • sulforaphane
  • Curcumin
  • quercetin
  • ginseng
  • (R)-alpha-lipoic acid
  • Hydrophilic oxidized derivatives of Lycopene
  • N-Acetylcysteine
  • DHEA
  • garlic
  • β-lapachone
  • pterostilbene
  • resveratrol
  • apigenin
  • zinc

 

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The whole reasoning sounds very suspect to me. There are no clearly identified anti-aging pathways. There are proteins associated with aging processes, though in most cases the precise role is still under investigation and in most cases it is not clear whether manipulating them would reverse aging processes (or perhaps, cause cancer by influencing apoptotic pathways, for example).

Even more worrying, they observe inflammation and then, without any evidence, make the jump to a number of pathways which for the most part just regulate basic cellular functions such as cell growth and metabolism. It is not mentioned that they monitored anything related to aging at all, just inflammation, and the rest is just pure speculation. Anyone actually involved in research would not classify what followed as theory, but pure speculation.

NMN has shown some beneficial effects, but specific to vascular aging in rodents. And there are things one could monitor there. However, I am highly suspicious of any report where folks apparently just label arbitrary pathways as anti-aging pathways and exhibit a poor understanding of how science is normally conducted and presented.. It really looks too much like a snake oil sales pitch.

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