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DNA Methylation, Aging, And Cancer

Discussion in 'Ray Peat Topics' started by haidut, Nov 19, 2013.

  1. haidut

    haidut Member

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    Hi all,

    Ray Peat has talked about this in some of his articles, and mentioned some specific techniques one can use to combat aging. This article talks about the relationship between the levels of methylation, aging, and cancer. As you suspect, with time methylation increases the risk of developing cancer and it seems to be one of the very hallmarks of aging. In fact, the article talks about how mature cells can be turned into "stem" cells by resetting the "epigenetic clock". Here is what Ray said:
    http://raypeat.com/articles/articles/co2.shtml

    "...The main mechanisms of epigenetic effects or “imprinting” are now known to involve methylation and acetylation of the chromosomes (DNA and histones)."
    "...Restriction of methyl donors causes demethylation of DNA".

    So, demethylation is desirable because it resets the "epigenetic clock" as mainstream science likes to refer to the process. Another potent method is to increase levels of CO2 or take niacinamide.

    Here is a recent article supporting Ray's views:
    http://www.fastcompany.com/3021694/this ... n-of-youth

    "...For example, Horvath discovered that across the board, healthy breast tissue measured two to three years older than the rest of a woman's body. And for women with breast cancer, the tissue adjacent to the tumor was 12 years older and the tumor itself was 36 years ahead of schedule. This advanced tissue age could explain why age is a huge risk factor for developing cancer."
    "...The procedure used for turning mature cells into stem cells resets the epigenetic clock to zero."

    Again, another example of the aging-cancer paradigm and how one seems to be just an accelerated form of the other, or more correctly cancer being a failed attempt at rejuvenation. Also, breast being "older" than other tissues probably has to do with the higher levels of estrogen in them.

    Just to summarize - methylation can be thought of as a direct measure of aging (or cancer potential) and reversing it is thought to be beneficial both for anti-aging and anti-cancer purposes. Baking soda, bag breathing, sugar (and efficient metabolism for its conversion to CO2), acetazolamide, niacinamide are all methods that are known to directly cause demethylation.

    Finishing up with a quote from Ray's article:
    "...Moderate methionine restriction (for example, using gelatin regularly in the diet) might be practical, but if increased carbon dioxide can activate the demethylase enzymes in a controlled way, it might be a useful treatment for the degenerative diseases and for aging itself. "
     
  2. jag2594

    jag2594 Member

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    I dont think ray peat considers aging the same as getting old.
     
  3. OP
    haidut

    haidut Member

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    Can you elaborate please? The term "getting old" could mean several things. For instance, we all get chronologically old and there is no way to stop that, even by traveling at the speed of light. From our perspective, time will always pass. So in that respect, aging and getting old are different. In what additional ways do you think Ray sees them as different?
     
  4. jag2594

    jag2594 Member

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    I meant Years.

    He gives the example in his book generative energy that scientist believe(d) that egg "run out", but it was really estrogen.
     
  5. OP
    haidut

    haidut Member

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    I think we are saying the same thing - i.e. Ray Peat believes that biological aging and chronological aging are not the same thing, and in fact chronological aging is just convenient to use/measure since so far the two types happened to coincide. But if a person is healthy in the Peat sense of the word (not aging biologically and super-metabolic) then it does not matter how old he/she is chronologically. I guess if it ever gets to the point of reversing aging, then language will have to change as well. We won't say someone aged since it would be ambiguous, but we will rather say someone "de-healthed" or "de-metabolized" or "patho-metabolized" or whatever.
    Maybe even do away with the aging paradigm altogether and just say someone "oxidized" (healthy) or "reduced" (unhealthy):)
     
  6. Milklove

    Milklove Member

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    Ray once mentioned in an interview that stressful events can lead to a special imprint and that this can even effect future generations, but a "hyper-nourishing" environment could erase this imprint.
    It seems like he was talking about the effects of (psychological) stress on methylation.

    I just did a very quick search on stress and methylation and found a lot:
    http://www.sciencedaily.com/releases/20 ... 082709.htm
    http://www.nature.com/tp/journal/v2/n8/ ... 1277a.html
    http://www.ncbi.nlm.nih.gov/pubmed/16262207

    It seems like an anti-stress diet and anti-stress behaviour could protect us from unwanted DNA methylation and as a result from aging and the associated symptoms. Ray Peats advice is always anti-stress, so that is another win for him! :)
     
  7. pboy

    pboy Member

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    I agree haidut. Old is just a word used to describe people who are noticeably becoming sick or weak. The chronological age isn't actually related, it just seems correlated but its chance and not actually dependent. I suppose there could be a word for a woman past the age of being able to give birth, but as for men...I agree, its simply healthy or not. In that same respect, you could say an unhealthy kid is 'old but with potential'...lol
     
  8. DaveFoster

    DaveFoster Member

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    @haidut

    Do you think that methylfolate and methylcobalamin should be avoided due to their donation of methyl groups in favor of non-methylated B-vitamins?
     
  9. OP
    haidut

    haidut Member

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    Possibly yes, but I think folic acid and B12 have other issues beyond just methylation. Both of them have been linked to cancer in adult and the recent studies seem to be more and more towards causal link. It is one of the reasons I don't have these two vitamins in Energin.
     
  10. DaveFoster

    DaveFoster Member

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    I understand folic acid rather than folate, but B12? I've heard so many good things about supplementing with it, but I guess that's no valid case.

    Without B12, do you think it would be wise to avoid related vitamins, such as B2 for example? I know you have no problem with B6 as P5P in smaller amounts (5 mg/day).

    Elevated Plasma Vitamin B12 Levels as a Marker for Cancer: A Population-Based Cohort Study

    This study seems to be what you're referring to. Could it be that elevated serum Cbl occurs during systemic inflammation in the same way that hypercalcemia develops in the presence of calcium deficiency and osteoporosis?
     
  11. OP
    haidut

    haidut Member

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    Yes, this is one study but there are more like it. Some cancers cell lines have been found in the lab to thrive on high concentrations of B12. The HeLa cell line is one example. So, until we know more I would not take B12 as a supplement unless there is proven deficiency. B2 has never been shown to be either correlated with or contributing to cancer. In fact, B2 deficiency is a known cause of esophageal cancer. That type of cancer developed most often in alcoholics, who are always deficient in B2 and sometimes in B1.
     
  12. DaveFoster

    DaveFoster Member

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    Thanks for the info. So it seems B1, non-methylated B2, B3, B6 (as P5P), biotin are safe to supplement. Non-methylated folate (not folic acid) and B5 (pantothenic acid) are still up for debate.

    Here's an interesting journal article on B-vitamins and cancer: http://cancerres.aacrjournals.org/content/2/11/752.full.pdf

    "That cancer cells are characterized by a high fermentation and low R.Q. has been known for many years. Rccent investigations of the enzyme systems in cancer tissues have not demonstrated that any of thc enzymes studied were significantly increased in accord with the greater fcrmcntative activity of the cancer cells. Nicotinic acid, for example, which is known to be an important part of many enzymes concerned with metabolic transformations of carbohydrate, has been shown to be low, rather than high, in cancer tissues (I5). Similarly, the results indicate that the incrcased glycolysis of cancer tissues cannot be associated with high riboflavin (io) or high biotin (9) content. This laboratory is embarked upon a program which has for one of its main objectives thc study of the rolcs which may be played by the B vitamins in cancer, and the distribution of pantothenic acid is the particular concern of this paper. The fact that there are indications that pantothenic acid may function as a catalyst in carbohydrate metabolism (If, 18) makes it particularly urgent that we survcy its role in cancer, where the carbohydrate metabolism differs from that of noncancerous tissues.

    Since pantothenic acid is so new, it is not surprising that there is little in the cancer literature about it. Morris and Lippincott (5) studied the effect of pantothenic acid deficiency on the growth of spontaneous mammary carcinoma in C3H mice and found that the tumor growth rate was retarded. This indicated that the tumors actually require the vitamin for growth and was confirmed by the resumption of tumor growth when pantothenic acid was added to the diet. If the pantothenic acid requirement of the tumor should be sufficiently great, then a proper deficiency of this element in the diet might retard or completely inhibit the growth of the tumor without seriously interfering with the metabolic activities of the host. Howevcr, Morris and Lippincott concluded that the pantothenic acid deficiency interfered so seriously with the host's nutrition that the procedure was without practical application in tumor therapy.

    In an interesting series of experiments, Lewisohn and his coworkers (2) recently reported that the injection of calcium pantothenate along with yeast in mice of the Rill strain led to a considerable reduction in the number of takes of mammary carcinoma 2163 transplants. The percentage of non-takes reported was 48 as compared with 2o for the yeast alone and 5 for the control mice.

    These results indicate that cancerous tissues probably do not have any greater need for pantothenic acid than do noncancerous tissues, but much more work is necessary before final conclusions can be drawn." - B Vitamins in Cancerous Tissues IV. Pantothenic Acid (p. 752)

    The retardation of tumor growth from withdrawing pantothenic acid reminds me of the role of IGF-1 as a tumor promoter, but also as a generally protective substance. Other studies show protective effects from calcium pantothenate.

    It seems that pantothenic acid may be safe to supplement. I can't seem to find any non-methylated forms of folate besides folic acid, (which is to be avoided).

    What do you think about B5?
     
  13. OP
    haidut

    haidut Member

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    I think that study is a very good answer to all the questions why I don't have B5, folic acid and B12 in Energin. So, thanks for posting it!
    Another reason for not including B5 is that virtually nobody is deficient in it, similar to iodine. It is added to pretty much every processed food, including the "artisan" breads everybody seems to be so fond of lately.
     
  14. supernature

    supernature Member

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    Wonder why they want to feed the people with iodine.
    No shout out at all on B4, B8, or they seems to be pretty individual regarding supplementation?
     
  15. OP
    haidut

    haidut Member

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    There is no agreement on what B4 is. There are at least 4 very different substances that vie for the title. As far as B8, I don't think it needs to be supplemented with as people can synthesize it from sugar.
     
  16. thegiantess

    thegiantess Member

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    I find this whole thing concerning and confusing. I have a complicated history with B12 specifically and it has caused me to go back and forth between supplementing and not. I have a history of veganism that have me a wicked deficiency, but I didn't realize it until years after I stopped the diet. Then I did the whole 23 and me thing and discovered a lot of MTHFR mutations. So I started getting b12 blood tests somewhat regularly just to see where I stood and if the mutations were having any effect. In the absence of supplements my b12 is always, always high. I have never gotten a straight forward answer as to why this might be, but a naturopathic doctor told me once that he thought I had a functional deficiency wherein my body can't use b12 efficiently so it doesn't recycle quickly and therefore shows high in my blood. When I supp b12 I do feel more energetic and some other things go away, but the cancer connection is deeply concerning.
     
  17. DaveFoster

    DaveFoster Member

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    That does seem confusing. Maybe just eating food sources high in B12 would be optimal and surpass the MTHFR mutation, such as liver and dairy products.
     
  18. supernature

    supernature Member

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    I should clarify my prev msg, i meant choline and inositol. Arent they important for methylation, demethylation of methionine ?
    You need choline to make DMG, and TMG is important for remethylation of Homocysteine. Maybe egg yolkes are a good source of lecithin, choline and other good stuff, as some not so good as well ?

    "Vitamin B16: dimethylglycine (DMG)[44] is synthesized by the human body from choline. - Wiki"

    "Choline is the precursor molecule for the neurotransmitter acetylcholine, which is involved in many functions including memory and muscle control. Some animals must consume choline through their diet to remain healthy. To humans, choline is an essential nutrient, as its role in reducing the risk of neural tube defects, fatty liver disease, and other pathologies has been documented.[6] Furthermore, while methionine and folate are known to interact with choline in the methylation of homocysteine to produce methionine, recent studies have shown that choline deficiency may have adverse effects, even when sufficient amounts of methionine and folate are present.[2][6] It is used in the synthesis of components in cell membranes. - Wiki"

    "Yet, Inositol, when present as phytate, is not directly bioavailable to humans in the diet, since it is not digestible. Some food preparation techniques partly break down phytates to change this. Inositol as it occurs in certain plant-derived substances such as lecithins, however, is well-absorbed and relatively bioavailable.
    Vitamin Bm: myo-inositol, also called “mouse antialopaecia factor.” -
    Wiki"
     
  19. OP
    haidut

    haidut Member

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    Google "Ray Peat choline" and "Ray Peat inositol". I think you will find the answer at least to the choline question.
     
  20. supernature

    supernature Member

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    Yes it came out 1 thread regarding eggs and choline, thanks!
    So can we assume that DNA Methylation has anything to do with One carbon metabolism ?
    Should we have to avoid folates actually or the deficiency is more harmful, regarding cancer for ex. ?
     
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