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Decline In Mitochondrial Function Is What Triggers Cancer

Discussion in 'Scientific Studies' started by haidut, Oct 10, 2014.

  1. haidut

    haidut Member

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    According to this study, the process of mitchondrial function decline, as seen in aging, creates a state of chronic hypoxia by inducing HIF-1 (which also happens to powerfully promote cancer). In fact, the following quote form the study reads like it could have been written by Ray Peat himself.

    http://www.cnd.mcgill.ca/~ivan/age-reve ... mpound.pdf

    "...Next, we sought to understand how SIRT1 regulates mitochondria independently of PGC-1alpha. Analysis of SIRT1 KO animals indicated that genes involved in glycolysis were upregulated, with increased lactate levels and a switch from slow-twitch oxidative fibers to fast-twitch glycolytic fibers. These metabolic changes were reminiscent of Warburg remodeling of metabolism in cancer cells, which is known to be mediated, in part, by the stabilization of the transcription factor HIF-1."

    The mitochondrial decline process is mediated through falling levels of NAD+ and thus lower NAD/NADH ratio, putting the cell in a reduced state. The scientists used carolic restriction to raise NAD, which is something we know Ray does not endorse as he thinks the process will actually put the body in a stressed mode and further damage cells.
    However, as we know, niacinamide raises NAD levels and thus the NAD/NADH ratio so this could be another strategy in reversing the decline in NAD and NAD/NADH.
     
  2. Such_Saturation

    Such_Saturation Member

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    Re: Decline in mitochondrial function is what triggers cance

    I wonder if "explosive workouts" naturally benefit "fast-twitch" fiber.
     
  3. OP
    haidut

    haidut Member

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    Re: Decline in mitochondrial function is what triggers cance

    That's the part that concerned me a bit. Slow-twitch fibers are associated with endurance training and fast-twitch ones with weight lifting. Does the study suggest that things like walking and running are better for the mitochondria and cancer than resistance training? If yes, that would go against Ray's preference for building up muscle to burn fat at rest.
     
  4. Such_Saturation

    Such_Saturation Member

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    Re: Decline in mitochondrial function is what triggers cance

    It looks like they use ATP in the first second and phosphocreatine in the first ten or so seconds, so anaerobic without lactic acid. If we keep sets very short and give about three minute intervals we should be fine. One maximal repetition should necessarily deplete phosphocreatine. This is all from Wikipedia of course. Ray Peat only advocates slow movements with light weights as far as I know. He also claims that anything faster than walking pace would not be "aerobic" regardless of the type of fiber, at least in the real world.
     
  5. M Scott

    M Scott Member

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    Re: Decline in mitochondrial function is what triggers cance

    So if I understand the paper correctly decreased NAD+ increases the actions of HIF-1 which damages mitochondrial function, so the cell resembles a hypoxic cell but may not necessarily be low in oxygen?

    Thanks for linking this paper, it's quite interesting. I've been doing a lot of research on hypoxia's effect on cancer by increasing HIF-1, damaging mitochondria, and leading to lactic acid glycolysis (helping explain the Warburg effect) but this seems to provide an alternative road to this end.

    I find the explanation that cancer is driven heavily by a destructuring of the cell's structure a compelling mechanism behind many of these observations but it's hard to find studies with methods designed to confirm this. Does anyone know of some good ones?
     
  6. Suikerbuik

    Suikerbuik Member

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    Re: Decline in mitochondrial function is what triggers cance

    M Scott, basically reduced NAD+/NADH ratio means your electron transport chain isn't functioning well. Also ask Such_Saturation, he made some post recently one with a paper called "energy management - a critical rle in cancer induction" :).
     
  7. M Scott

    M Scott Member

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    Re: Decline in mitochondrial function is what triggers cance

    Suikerbuik - ah yes, that makes sense now, since the ECT turns NADH into NAD+. So I wonder what factors are responsible for this loss of function. This paper seems to focus on aging as a cause and NMN as a solution but I'm sure there's a lot more to it.
     
  8. Such_Saturation

    Such_Saturation Member

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    Re: Decline in mitochondrial function is what triggers cance

    I think you're right! That Garland J. is particularly progressive in his explanation of the "new" boatload of evidence that is being thrown around. Konradin Metze reviews some experiments about structure that target the tidiness of nucleus packing. It's hard to do these experiments because you would want ideally a three-dimensional scan of the DNA which needs very advanced techniques. Also, compression of this data means you can't use the mathematics to extract a meaningful result anymore so ideally you need raw data to show the fractal characteristics. You can find them here viewtopic.php?f=10&t=4535
     
  9. Suikerbuik

    Suikerbuik Member

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    Re: Decline in mitochondrial function is what triggers cance

    That's what Peat's work is all about :), pufa, low thyroid, chronic inflammation (allergies for example), serotonin, toxins (including excess iron), stress, excess estrogen, ...
     
  10. charlie

    charlie The Law & Order Admin

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    Re: Decline in mitochondrial function is what triggers cance

    Ray Peat talks about NADH in the latest radio interview on "Longevity".

    viewtopic.php?f=41&t=5042
     
  11. Peata

    Peata Member

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    Re: Decline in mitochondrial function is what triggers cance

     
  12. Peata

    Peata Member

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    Re: Decline in mitochondrial function is what triggers cance

    Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

    William W Wheaton, Samuel E Weinberg, Robert B Hamanaka, Saul Soberanes, Lucas B Sullivan, Elena Anso, Andrea Glasauer, Eric Dufour, Gokhan M Mutlu, GR Scott Budigner, Navdeep S ChandelCorresponding Author

    The Feinberg School of Medicine, Northwestern University, United States; University of Tampere, Finland
    DOI: http://dx.doi.org/10.7554/eLife.02242Published May 13, 2014 Cite as eLife 2014;3:e02242
    Abstract

    Recent epidemiological and laboratory-based studies suggest that the anti-diabetic drug metformin prevents cancer progression. How metformin diminishes tumor growth is not fully understood. In this study, we report that in human cancer cells, metformin inhibits mitochondrial complex I (NADH dehydrogenase) activity and cellular respiration. Metformin inhibited cellular proliferation in the presence of glucose, but induced cell death upon glucose deprivation, indicating that cancer cells rely exclusively on glycolysis for survival in the presence of metformin. Metformin also reduced hypoxic activation of hypoxia-inducible factor 1 (HIF-1). All of these effects of metformin were reversed when the metformin-resistant Saccharomyces cerevisiae NADH dehydrogenase NDI1 was overexpressed. In vivo, the administration of metformin to mice inhibited the growth of control human cancer cells but not those expressing NDI1. Thus, we have demonstrated that metformin's inhibitory effects on cancer progression are cancer cell autonomous and depend on its ability to inhibit mitochondrial complex I.

    Full Text
     
  13. thebigpeatowski

    thebigpeatowski Member

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    Re: Decline in mitochondrial function is what triggers cance

    Eegads, I sure wish I could understand all of this. Unfortunately I don't have anywhere near the brain capacity...sigh.

    So Peata, you have taken Metformin and also gone for periods without it , correct? What differences do you notice? How is your gut flora affected by Metformin? This stuff fascinates me, I just wish I could grasp it better.
     
  14. OP
    haidut

    haidut Member

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    Re: Decline in mitochondrial function is what triggers cance

    I posted some stuff on Metformin months ago. As far as I can remember it was not very positive in light of Peat's ideas and he has also said he does not recommend using it. I think most of the negatives come from the fact that the drug increases fat oxidation, which will increase the tress response even more. Fr diabetes, instead of reducing gluconeogenesis and increasing fat oxidation, you need a drug that inhibits fat oxidation and sensitizes the cells to glucose. In Peat land, the combination of taurine (insulin mimetic) and niacinamide (fatty acid oxidation inhibitor) should achieve these two goals. Niacinamide is well known on this forum, but if you want more info on taurine and its anti-diabetic effects just Google "taurine insulin". Or read this post as a start:
    http://suppversity.blogspot.com/2011/08 ... sulin.html
     
  15. Peata

    Peata Member

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    Re: Decline in mitochondrial function is what triggers cance

    Haven't noticed anything either way over the last several years. I went off it back in April. Then went back on it in Aug or Sept. just to see if it would do anything, but no effect.
     
  16. Peata

    Peata Member

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    Re: Decline in mitochondrial function is what triggers cance

    I stopped taking it today.
     
  17. Peata

    Peata Member

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    Re: Decline in mitochondrial function is what triggers cance

    Sounds like an energy drink per day would be good (plus it has the caffeine). I have some niacinamide around but stopped taking it a while back. Taurine, I'll have to look and see if I have any. I wonder about taking the doses 3 x per day like I was doing with metformin.
     
  18. Amazoniac

    Amazoniac Member

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    Metabolic Reprogramming: A Cancer Hallmark Even Warburg Did Not Anticipate

    "The recognition that proliferating cells do not maximize ATP production through mitochondrial oxidative phosphorylation has contributed to the continuing misconception that proliferating cells, particularly cancer cells, do not utilize mitochondria. In fact, most cancer cells and proliferating normal cells still derive a significant fraction of their ATP through oxidative phosphorylation. However, in proliferating cells, in contrast to quiescent cells, this oxidative phosphorylation-dependent production of ATP appears secondary to the use of mitochondrial enzymes in the synthesis of anabolic precursors."

    Cancer: disorder and energy
    "What has received little appreciation since the work of Krebs and his colleagues is that for many proliferating cells, the major problem is not how to maximize ATP yield, but rather how to maximize the flux of carbon into macromolecular synthetic pathways. In fact, it was first demonstrated in 1973 that glycolysis in proliferating cells is limited by the rate of ATP consumption and not ATP production, as glycolytic enzymes can be inhibited when ATP levels are high (Scholnick et al., 1973). Recent work has revisited how proliferating cells maintain glycolytic flux by either minimizing ATP production or enhancing ATP consumption."


    "Unlike ATP, cytosolic NADPH might be limiting for cell proliferation. It is critical for providing reducing equivalents for fatty acid and cholesterol biosynthesis, as well as for modulating oxidative stress."
     
  19. EndAllDisease

    EndAllDisease Member

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    Yeah absolutely. Cancer is not complicated nor is it anything to fear.
    Expose a cell to any poison that disables the highly-sensitive cytochrome c oxidase enzyme and the cell will revert to the cancer metabolism. The other way to cause cancer is by not providing the cell with the vitamin or mineral it needs to produce the enzymes that power metabolism.

    The only thing to fear is anybody saying they want to cut you with a knife, inject poison into you or direct ionizing radiation at your body.
     
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