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Reversal of aging - resveratrol, nicotinamine riboside and nicotinamide mononucleotide

Discussion in 'The New Monster Thread' started by Da-mo, Nov 7, 2014.

  1. Da-mo

    Da-mo Gold

    After following a tortuous path beginning with a search on nicotine and molybdenum, then exploring nicotinic acid and then finding out about nicotinamide mononuclotide (NMN), it seems they have been able to use NMN to reverse aging in mice and have started human trials. They were able to reverse the biological age of the mice within one week from 22months to 6 - equivalent to taking a 60yo to 20yo in human years.

    Apparently resveratrol has similar effects although much less potency . . . . . anyway, a few links to explore

    http://www.resveratrolnews.com/long...oduced-in-recent-animal-laboratory-study/862/

    http://www.cell.com/abstract/S0092-8674(13)01521-3
     
    Brother John likes this.
  2. Jack Kruse

    Jack Kruse Administrator

    resveratrol works on Mo-flavinoid pathways to re engineer gut flora. Have a look at the Quilt......you'll see resveratrol gets its own levee. Read Tensegrity 8 and you'll see me mention Mo flavin enzyme called AO. BOOM
    I gave you the answers 5 yrs ago in the quilt..........

    Now I am giving you the play book of how I unlocked it.
     
  3. NeilBB

    NeilBB New Member

    Jack has talked about this paper and Sinclair in past. Josh probably remembers where...

    (Last word on Van Hagar, Damo.) Eddie was way too good to need a backup guitarist and Sammy wasn't at all comfortable performing without his guitar. BOOM. Hahaha.
     
    Shijin13, fitness@home and Da-mo like this.
  4. Jack Kruse

    Jack Kruse Administrator

    Sinclair's paper was linked in EE11-13 I believe. Awesome paper.
     
    Da-mo and NeilBB like this.
  5. Da-mo

    Da-mo Gold

    Great Blog Josh, - I already know some experts who need to read it. ;) Sending them the link.
     
    Josh (Paleo Osteo) likes this.
  6. thanks guys, feel free to leave comments
     
  7. I remember you saying the best resveratrol was in really pure amazonian chocolate. You mentioned this in one of your Q and A's about this time last year. I think last year and April. Oh? Could I be developing a Jack Kruse memory? Hmmm! I guess I have gained a few electrons from the Mitochondrial RX!
     
  8. Penny

    Penny New Member

    Pleiotropic mechanisms facilitated by resveratrol and its metabolites
    Barbara CALAMINI,*,1,2 Kiira RATIA,* Michael G. MALKOWSKI,† Muriel CUENDET,‡ John M. PEZZUTOBernard D. SANTARSIERO,* and Andrew D. MESECAR*,2
    Author information ► Copyright and License information ►

    The publisher's final edited version of this article is available free at Biochem J
    See other articles in PMC that cite the published article.

    Go to:
    Abstract
    Resveratrol has demonstrated cancer chemopreventive activity in animal models and some clinical trials are underway. In addition, resveratrol was shown to promote cell survival, increase lifespan and mimic caloric restriction, thereby improving health and survival of mice on high-calorie diet. All of these effects are potentially mediated by the pleiotropic interactions of resveratrol with different enzyme targets including COX-1 (cyclo-oxygenase-1) and COX-2, NAD+-dependent histone deacetylase SIRT1 (sirtuin 1) and QR2 (quinone reductase 2). Nonetheless, the health benefits elicited by resveratrol as a direct result of these interactions with molecular targets have been questioned, since it is rapidly and extensively metabolized to sulfate and glucuronide conjugates, resulting in low plasma concentrations. To help resolve these issues, we tested the ability of resveratrol and its metabolites to modulate the function of some known targets in vitro. In the present study, we have shown that COX-1, COX-2 and QR2 are potently inhibited by resveratrol, and that COX-1 and COX-2 are also inhibited by the resveratrol 4′-O-sulfate metabolite. We determined the X-ray structure of resveratrol bound to COX-1 and demonstrate that it occupies the COX active site similar to other NSAIDs (non-steroidal anti-inflammatory drugs). Finally, we have observed that resveratrol 3- and 4′-O-sulfate metabolites activate SIRT1 equipotently to resveratrol, but that activation is probably a substrate-dependent phenomenon with little in vivo relevance. Overall, the results of this study suggest that in vivo

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265359/

    Also, it discusses MO enzymes and aldehyde oxidase - good luck fathoming it:)

    https://books.google.com/books?id=o...v=onepage&q=molybdenum flavin enzymes&f=false
     
  9. Nittygrittydanny

    Nittygrittydanny New Member

    Show was better with DLR, but the music was kickass with Sammy. I vote Van Hagar!!!
     
  10. Mystic Rose60

    Mystic Rose60 Let the sun shine on you :))

  11. if the hallmarks of an anti aging system are increase in the NAD+/NADH ratio, and NAD+ inhibits SIRT1, then the Resveratrol (activation of SIRT1) route needs to be questioned.
     
    Mystic Rose60 likes this.
  12. Mystic Rose60

    Mystic Rose60 Let the sun shine on you :))

  13. yes, the idea of SIRT1 is to replenish NAD+ in times of stress. once NAD+ is re-elevated, SIRT1 is inhibited.


    2 things are important


    a) Resveratrol is Estrogenic (anabolic/proliferative)

    b) Resveratrol is SIRT1 Enhancing


    People often support Resveratrol by ignoring a, and thinking b is good - it is the CONTEXT that matters...SIRT1 is upregulating tha machinery that allows the cell to make maximum use of minimal substrates - in this regard SIRT1 is a stress regulatory enzyme, and it should have high activity when in high stress (starvation etc) and low activity at other times (fed state - this makes me laugh at the notion of dribking resveratrol enhanced wine, which ALWAYS will be happening in the well fed state!!) - Dean Kilby alert.


    Resveratrol activates SIRT1

    Niacinamide Suppresses SIRT1 (as a side effect of enhancing NAD+)


    IN vitro studies show that resveratrol “works” – ie with cancer cell apoptosis

    IN vivo – resveratrol shown to be estrogenic
     
  14. nonchalant

    nonchalant Silver

    Hi Josh! In Ubiquitination 17, Jack mentions that nicotine (and not niacin or niacinamide) increase both NAD+ and SIRT1. He also discusses the benefits of increasing both.
     
  15. context is everything.

    niacin and niacinamide both increase the NAD+ pool

    NAD_NIacinamide.png

    SIRT1 activation is a sort of switch that indicates availability of easily available resources.

    The lack of quick energy substrates (like glucose) demands higher SIRT1 activation, which in turn, stimulates programs that mobilise energy from various stores, while upregulating fatty acid metabolism.

    This is thus going to be a very dynamic sate, with the present state of the person having a huge factor in which compound is going to work best.
    For example, immediately after a significant amount of exercise, SIRT1 is going to be up-regulated, presumably due to the energetic stress of consuming substrate.

    The hallmark of the cancer state is a compromise in the ability to oxidise "fast substrate" like glucose, and forcibly up-regulating SIRT1 using compounds like resveratrol may be helpful in preventing the cell from panicking due to the lack of energy.

    However, the opposite can also be said to be true, that by forcibly increases NAD+ pool through nicotinamide treatment, that the "cancer state" is reversed. This has mixed results, which IMO, has to do with the up- and down-stream reasons for cancer.


    Now, when we are dealing with Nicotine, which stimulates the Nicotinic-Acetylcholine receptors, we have a "forced excitatory state".

    Whether the cell should be relaxed (via Sirtuin activation) or primed (via fast NAD+ replenishment), is going to depend on the existing energetic capabilities of the cell.
     
  16. And of course, circadian variation will play a role. Midday, after significant light exposure and enough food, would generally be a well-fed, low SIRT1 state, while early morning and evenings would be the opposite.
     
  17. Bump on this one please :)

    @Josh (Paleo Osteo) from what I understood from your explanation is...Resveratrol may be beneficial in the morning and evenings and NMN during the afternoon period?
     

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