115 replies to this topic

[Hedrock]

That's absurd!

By mathematical division of the body total cells through the dying cells you think every cell is replaced one time a year?

Now I see you are making fun of me. In the beginning I thought you mean it serious!

Edited by Hedrock, 12 May 2010 - 07:58 PM.

[Hedrock]

Can you image there are some cell types which are replaced on a weekly base?

What would the consequences to your calculation be?

Edited by Hedrock, 12 May 2010 - 08:03 PM.

[urba]

That's absurd!

By mathematical division of the body total cells through the dying cells you think every cell is replaced one time a year?

Now I see you are making fun of me. In the beginning I thought you mean it serious!

I've just stressed, that fat rich cells - ADIPOCYTES lives aproximately 10 years. The other kind of cells has the other duration of life. Blood cells lives much shorter time, I hope. It was opinion form Wikipedia, that all the cells during the yar are changed by the new ones (perhaps some only very average idea). You stressed, that this is incorect, becouse of energy usage and I agree. We need more information about this problem. My idea is that the main target in reunivation strategy are the stem cells becouse they reborn lost becouse of appoptosis human body cells,

Edited by urba, 13 May 2010 - 08:50 PM.

[urba]

What about the target DNA methylation control?

The essence of my work ist this:

Epigenetic initialisation be Resveratrol + EGCG + Honokiol, the king supplements! EGCG could be replaced by parthenolide.

These 3 mighty supplements involve DNA (De-)methylation + histone acetylation + histone (De-)phosphorylation.

The reprogramming itself is started by hormones: estrogens + DHEA (the both most important reprogramming starters),D3, melatonin, phytoestrogens and ecdysteroids.

To keep telomeres long, cycloastragenol or astragaloside-4 can be used.

Thats all I have. Now help me to come forward. It's your turn,

I've just red that some vegetables are rich of nature-estrogen genistein. So, is it necessary to make injections? Could they be changed by special food rich of soya, parcial plus some herbs and fruits?

[VidX]

Is this somehow relevant (talks about specific methylation and a significance in aging, etc..): http://www.immortalh...ifferentiation/

Edited by VidX, 03 July 2010 - 10:54 PM.

[Gern]

That's absurd!

By mathematical division of the body total cells through the dying cells you think every cell is replaced one time a year?

Now I see you are making fun of me. In the beginning I thought you mean it serious!

I've just stressed, that fat rich cells - ADIPOCYTES lives aproximately 10 years. The other kind of cells has the other duration of life. Blood cells lives much shorter time, I hope. It was opinion form Wikipedia, that all the cells during the yar are changed by the new ones (perhaps some only very average idea). You stressed, that this is incorect, becouse of energy usage and I agree. We need more information about this problem. My idea is that the main target in reunivation strategy are the stem cells becouse they reborn lost becouse of appoptosis human body cells,

Then how do you account for the well established evidence that telomeres get shorter as people age. If cells are being replaced that fast wouldn't it be fast enough to counteract the relatively slow rate of telomere shortening.

[DorianGrey]

Hi,

I haven't had the time to truly research this entire thread but I am very interested in DNA Methylation reprogramming. Epigenetics seems to hold one key for anti-aging, telomer attrition/elongation most likely matters in some types of cells and attrition accelerates with aging (immune system, hematopoeitic stem cell), so DMR could be also one way to ameliorate that. I am also fascinated by the current investigations into the blood factor GF11, which may have immediate effects. 

Epigenetic target:

DNA methylation 

Histone deacetylation

Histone methylation state -- this is the one target I only learned about recently. It's quite complex but the methylation state of certain conserved lysines can be 0,1,2 or even 3.

 

Currently I try to up my Butyrate (mild HDACi) (butter has 3-4%, I drink 5-10g high quality butter dispersed in a foamy cup of fresh coffee). I do also eat fermented foods and drinks on a regular basis (Natto, Kefir, Kombucha, Kimchi) which either contain Butyric acid or gut bacteria that enable the production.

For methylation, I use a multivit with 400micro folate in the morning (has all B-vitamins and many others), 750 micro Methylfolate, one 750mg TMG in the morning (probably good idea regarding the butter), another 400micro folate for lunch or a little later. Also healthy diet with lots of greens. And a bunch of other stuff that might support the idea like omega-3's and green tea. Any ideas to further improve that stack? I don't want to go higher with the cheap folate as there have been reports >1mg a day isn't so good anymore. I sometimes use a flush free Niacine (250mg) but I am hesitant to use Niacine too often and I remember other forms (NAD+) are quite expensive. 

 

 

Edited by DorianGrey, 27 August 2014 - 01:42 PM.

[DorianGrey]

 

 

So here are some of the natural substances I already take and which might have epigenetic potential:
... EGCG,

 

 

I just learned EGCG is an inhibitor of DNA methylation, not really what we want for anti-aging?

[HighDesertWizard]

I will read this entire thread but, within the next week, I will. I see that it is concerned with Reprogramming of the Epigenome. We seem all to agree that Epigenetic Change is pervasive and, yet, we don't know the first thing about how to Consciously and Deliberately trigger Positive (for Health) Epigenetic Change.

 

Still, I have an personal, n=1, anecdotal story that, I believe, is relevant to the discussion. I'm also keen to get feedback on a hypothesis about something I once experienced.

 

I believe I once triggered significant and positive Epigenetic change in myself by accident...

 

For years, I wondered about what had happened to me. And then, once I learned a bit about the science of Epigenetics, I finally had an Explanation of what Might have occurred. I'm not a scientist but, because of my experience, I am interested in Conscious and Deliberate attempts to Trigger Positive Epigenetic Change...

 

Around about 2006, my early stage Carpal Tunnel Syndrome (CTS) symptoms began to worsen. I purchased wrist braces for sleep to deal with waking up with both wrists numb until I shook my hands for about a minute to get feeling back. CTS runs in my immediate family: my father had CTS surgery on one wrist and a sister on both wrists.

 

I had been doing do-it-yourself, n=1, experiments on myself for a decade. At that time, I decided to mega-dose on an anti-inflammatory herb called Boswellia (and specifically the AKBA, 5-Loxin, formulation), 2 grams a day for a reason unrelated to the CTS.

 

If you look at this closely, you'll quickly realize that a 2g/day dose of Boswellia [AKBA] is a big dose. Was I worried about toxicity? No, I'm happy to explain why I wasn't later. I made my own capsules from a 5-Loxin powder source I found on the 'net.

 

Within one week of my beginning this experiment, my CTS symptoms vanished. I mean they Vanished. It was amazing. I stopped the Boswellia [AKBA] dosing and the symptoms returned within about a week and I decided to try it again.

 

I did that same dose of Boswellia [AKBA]--5-Loxin specifically--again. My CTS symptoms vanished a second time after about a week. I continued that dose for one month and then stopped completely.

 

My CTS symptoms were gone and have never returned.

What's the Explanation for what happened to me? Like I mentioned above, I believe the best explanation is that I triggered Positive Epigenetic Change...

• There are several studies that show Boswellia can trigger Epigenetic Change and/or Gene Expression of ProInflammatory Genes. 
• ​There are several studies that show MPPs (Matrix Metalloproteinases) are implicated in CTS.
• There are several studies that show Boswellia can have a Positive Impact on MMP Expression.

I'll be happy to provide links to these studies as desired/needed. In the meantime, I wanted to share my story and get feedback about it.

 

Thoughts?

Edited by wccaguy, 01 September 2014 - 04:51 PM.

[HighDesertWizard]

In my previous post, I suggested that my early stage CTS symptoms may have vanished in a very short time via epigenetic processes through Mega Doses of 5-Loxin - Boswellia [AKBA]. In this post, I'll provide links to studies that suggest this hypothesis is not without foundation.

Again, let me state, I'm not a Scientist. My formal education in Science is limited. But I have spent and do spend considerable time reading Longevity related abstracts.

First... Are there studies that show that MMPs are implicated in CTS?  Answer: Yes.

• MMP-3 is implicated in CTS.
• MMP-2 expression is associated with rapidly proliferative arteriosclerosis in the flexor tenosynovium and pain severity in carpal tunnel syndrome
• and there are more...

 

Second... Are there studies that show Boswellia impacts/inhibits MMP-3 and MMP-2 expression? Answer: Yes.

• A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee

In this study, MMP-3 inhibition occurs with 5-Loxin [AKBA] in a dose dependent manner. And, btw, the optimal dose was not found in this study. Check Figure 3.

• Regulation of Vascular Responses to Inflammation: Inducible Matrix Metalloproteinase-3 Expression in Human Microvascular Endothelial Cells Is Sensitive to Antiinflammatory Boswellia

Third... Are there studies that show Boswellia can trigger Epigenetic Change and/or Gene Expression of ProInflammatory Genes? Answer: Yes.

• Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

 

Fourth... Are there studies that show MMPs--and, in this case, MMP-3--is regulated by Epigenetic means? Answer: Yes.

• The role of DNA hypomethylation in the control of stromelysin gene expression

Please note that, in this study, MMP-3 is regulated by DNMT gene expression.

 

 

Fifth... Are there studies that show an impact of Boswellia on DNMT gene expression?Answer: Yes.

• Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

This study found that Boswellia [AKBA] inhibited DNMT activity

 

I feel uncomfortable posting all this because I'm certain I don't have knowledge to understand all the issues and/or whether I am way off in speculating about an Explanation for my CTS experience.

I look forward to any discussion of these issues!

Edited by wccaguy, 01 September 2014 - 06:02 PM.

[Avatar of Horus]

I am interested too. My current focus is the EZH2, Enhancer of Zeste homolog 2 protein, which is a histone lysine methyltransferase, but it controls the activity of the DNA methyltransferases.
 

The Polycomb group protein EZH2 directly controls DNA methylation
Viré et al. 2006. Nature
http://www.ncbi.nlm....pubmed/16357870
 
...EZH2 is required for DNA methylation of EZH2-target promoters. Our results suggest that EZH2 serves as a recruitment platform for DNA methyltransferases, thus highlighting a previously unrecognized direct connection between two key epigenetic repression systems.

 

...
Epigenetic target:
DNA methylation 
Histone deacetylation
Histone methylation state -- this is the one target I only learned about recently. It's quite complex but the methylation state of certain conserved lysines can be 0,1,2 or even 3.
...
And a bunch of other stuff that might support the idea like omega-3's and green tea. Any ideas to further improve that stack? ...

... 
I just learned EGCG is an inhibitor of DNA methylation, not really what we want for anti-aging?

Green tea contains EGCG:
Tea catechins' affinity for human cannabinoid receptors
Korte et al. 2010
http://www.ncbi.nlm....pubmed/19897346

I don't know the exact effect of Omega-3 on DNA methylation, but it can suppress EZH2 expression:
Dietary omega-3 polyunsaturated fatty acids suppress expression of EZH2 in breast cancer cells
Dimri et al. 2010, Carcinogenesis (3):489-95.
http://www.ncbi.nlm....pubmed/19969553

[HighDesertWizard]

I am interested too. My current focus is the EZH2, Enhancer of Zeste homolog 2 protein, which is a histone lysine methyltransferase, but it controls the activity of the DNA methyltransferases.

 

Many studies have found Curcumin to trigger Epigenetic Effects, including this study note an effect on EZH2.

 

http://www.ncbi.nlm....pubmed/20385124

[HighDesertWizard]

Fourth... Are there studies that show MMPs--and, in this case, MMP-3--is regulated by Epigenetic means? Answer: Yes.

• The role of DNA hypomethylation in the control of stromelysin gene expression

Please note that, in this study, MMP-3 is regulated by DNMT gene expression.

 

 

Fifth... Are there studies that show an impact of Boswellia on DNMT gene expression?Answer: Yes.

• Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

This study found that Boswellia [AKBA] inhibited DNMT activity

 

I'm now thinking that it's not the DNMT gene that was involved in what I experienced...

[Avatar of Horus]

I will read this entire thread but, within the next week, I will. I see that it is concerned with Reprogramming of the Epigenome. We seem all to agree that Epigenetic Change is pervasive and, yet, we don't know the first thing about how to Consciously and Deliberately trigger Positive (for Health) Epigenetic Change.

Still, I have an personal, n=1, anecdotal story that, I believe, is relevant to the discussion. I'm also keen to get feedback on a hypothesis about something I once experienced.
 
I believe I once triggered significant and positive Epigenetic change in myself by accident...
 
...

I'll be happy to provide links to these studies as desired/needed. In the meantime, I wanted to share my story and get feedback about it.
 
Thoughts?

 
A note: I don't know, but I think that you cannot expect much feedback on it - or anyone on any other idea/hypothesis, for that matter - not because it's good or bad, but because the small number of forum participants, and therefore also the limited knowledge/interest range.
 

Fourth... Are there studies that show MMPs--and, in this case, MMP-3--is regulated by Epigenetic means? Answer: Yes.

• The role of DNA hypomethylation in the control of stromelysin gene expression

Please note that, in this study, MMP-3 is regulated by DNMT gene expression.

Fifth... Are there studies that show an impact of Boswellia on DNMT gene expression?Answer: Yes.

• Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells

This study found that Boswellia [AKBA] inhibited DNMT activity[/size]

 
I'm now thinking that it's not the DNMT gene that was involved in what I experienced...

 
Why is that?

BTW, the green tea / EGCG and EZH2 can affect the regulation of the MMPs, by a way that is "independent of promoter DNA hypermethylation".
A related study about TIMP3, which can interact with e.g. MMP-2, -3, -9:

Epigenetic induction of tissue inhibitor of matrix metalloproteinase-3 by green tea polyphenols in breast cancer cells
Deb et al., Mol Carcinog. 2014
http://www.ncbi.nlm....pubmed/24481780

[treonsverdery]

Perhaps the original person that was researching how to custom methylate their genes has heard about s adnosyl methylcysteine as well as dimethylglycine both of these are  supplements  here is a link from after the topic started

 

DNA methylation
J Nutr Biochem. 2012. Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. This is the most extensively studied mechanism of epigenetic gene regulation. Increasing evidence indicates that DNA methylation is labile in response to nutritional and environmental influences. Alterations in DNA methylation profiles can lead to changes in gene expression, resulting in diverse phenotypes with the potential for increased disease risk. The primary methyl donor for DNA methylation is S-adenosylmethionine (SAM), a species generated in the cyclical cellular process called one-carbon metabolism. One-carbon metabolism is catalyzed by several enzymes in the presence of dietary micronutrients, including folate, choline, betaine and other B vitamins. For this reason, nutrition status, particularly micronutrient intake, has been a focal point when investigating epigenetic mechanisms. Although animal evidence linking nutrition and DNA methylation is fairly extensive, epidemiological evidence is less comprehensive. This review serves to integrate studies of the animal in vivo with human epidemiological data pertaining to nutritional regulation of DNA methylation and to further identify areas in which current knowledge is limited.

 

Front Aging Neurosci. 2013 Dec 5. DNA methylation, a hand behind neurodegenerative diseases. In this review, we have reviewed and summarized recent progress regarding DNA methylation in four major neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The studies of these four major neurodegenerative diseases conclude the strong suggestion of the important role DNA methylation plays in these diseases. However, each of these diseases has not yet been understood completely as details in some areas remain unclear, and will be investigated in future studies. We hope this review can provide new insights into the understanding of neurodegenerative diseases from the epigenetic perspective.

Trimethylglycine TMG and Dimethylglycine DMG
TMG, also known as betaine, is basically the amino acid glycine attached to three methyl groups. Dimethylglycine is similar to trimethylglycine, except it has two methyl groups. You may recall that a methyl group is a carbon attached to three hydrogen atoms (CH3). Both of these nutrients are powerful methyl donors. Methylation is an important factor in many biochemical processes in the human body. In chapter 9 I mentioned that the B vitamins folic acid and B12 lower levels of homocysteine, the harmful amino acid-like substance in blood which can cause hardening of the arteries and possibly damage brain cells. By reducing homocysteine levels, the risk for heart disease can be reduced. TMG and DMG are also known to reduce homocysteine levels and therefore could be helpful in reducing the rate of heart disease. It’s possible that as we age, the process of methylation becomes less effective and supplementation with TMG or DMG may provide health and anti-aging benefits.

 

from http://www.raysahelian.com/methyl.html  ( it might be an advertisement, it has peer reviewed journal references though)

Edited by treonsverdery, 11 September 2014 - 11:07 PM.

[Astroid]

Some have a bad gene and can not process Folate and obtain Methyl .. There is a test for that and one can now take MethylPro that resolves the problem.. A friend took it and it changed his life. It is available online. 

[DorianGrey]

Some have a bad gene and can not process Folate and obtain Methyl .. There is a test for that and one can now take MethylPro that resolves the problem.. A friend took it and it changed his life. It is available online. 

Actually, they still convert but at about 20% (half of the Italians half that mutation!) compared to the normal gene.

 

What I didn't have on my radar so far:

 

Methylated forms of Folate are not really helping because Folate is cycled multiple times in the body and the Methyl of course is used only once. You create a "sink" and according to a Podcast I listened to, one inactive form of folate actually removes methyl groups from accessible DNA - yikes.

 

I don't take additional folate anymore. My daily multi-vit already has 600microgram so that's more than enough, considering I eat a lot of spinach, kale etc. so really shouldn't supplement more.

 

I'd look more for B6 and B12 or more TMG now to keep Methylation levels high, but definitely not folate supplements.

[Astroid]

 

Some have a bad gene and can not process Folate and obtain Methyl .. There is a test for that and one can now take MethylPro that resolves the problem.. A friend took it and it changed his life. It is available online. 

Actually, they still convert but at about 20% (half of the Italians half that mutation!) compared to the normal gene....

 

 

 

That is good to know about the 20%.. An elderly man in his late 60's that I swap info with, and who takes supplements and eats right.. wrote and told me this year that he still felt bad and had no energy.. I thought that was odd as he had all sorts of medical test that show nothing..

 

I happen to send him a couple of Pharmacist Suzy Cohen's articles.. and one she mentioned the Folate gene problem.. He was tested and sure enough that was his issue..  He researched it and came up with the MethylPro and took it.  Later he wrote me 4 times about how great he feels now.

 

I wondered.. if he had this bad gene.. looks like it would have shown up before.. of course I assumed he had no ability to process Folate. So that explains the puzzle. 

 

MethylPro.com has seminars online for recurrent education for MDs and cheaper rates for the public.  They offer 1 mg, 5 mg, 10, mg & 15 mg versions of the MethyPro. I started taking the 5 mg myself a couple of months ago.. but did not notice any change..

 

I did observe earlier this year how much better I felt this year.. and thought about what supplements I had added.. Basically it was 500mg + of Magnesium Bicarbonate Water (absorbed at 50% vs 5% of Mag Oxide pills),  Biotin, Folate and Betain HCL last year. 

 

This year it has been MSM-Sulfur 1 rounded teaspoon 2 x /day, strong liquid Multi-Minerals form Vital Earth Minerals, SE-Methyl Selenium from Life Extension 200 mcg,  50,000 units of D3 at 2-3 x week, Super K by Life extension, and Iodoral Iodine. I also added 5 x 168 mg of Vitalzym Systemic Enzymes every morning. Vitalzym is used as a pain killer in Europe. 

 

Also I added Taurine amino acid for a muscle spasm. I found I had to add Arginine then for it to work with the Magnesium to stop them.     

Edited by Astroid, 06 October 2014 - 09:26 PM.

[HighDesertWizard]

<< snip >>

I believe I once triggered significant and positive Epigenetic change in myself by accident...

<< snip >>

 

... my early stage CTS symptoms may have vanished in a very short time via epigenetic processes through Mega Doses of 5-Loxin - Boswellia [AKBA]. In this post, I'll provide links to studies that suggest this hypothesis is not without foundation.

<< snip >>

 

Like an increasing number of others, I believe that most Adult Onset Health Disorders, by definition, have a specific Epigenetic cause. And I mean this in very specific health disorder contexts, e.g., in my Carpal Tunnel Syndrome (CTS) experience.

• In this post, I summarize a friend’s recent experience to date, following a path generally grounded in learnings from my experience with CTS and Boswellia.
• In my next post, I will circle back around and provide the scientific study reference links that led me to believe this path might work for her.
• I’ve spent a little time imagining a framework for evaluating study evidence to help with thinking through which similar health disorder contexts might be addressed in the future with this approach. If I can get it to a point that might add value, I’ll share it.

-------------------------------------------------

I have a mid-50s, female friend who who has suffered from Interstitial Cystitis (IC) for years. Recommended changes in diet would make a difference but have been difficult to follow consistently. And periods of stress would exacerbate the pain symptoms even when the proper diet was followed. To make a long story short, based on my own experience and research I summarize in my next post, my friend decided to do her own n=1 experiment to address her IC.

• In my next post, I’ll provide the reference study evidence that explains the rationale for using the Life Extension Super BioCurcumin product.

• My friend began by taking 1 capsule a day and increased the dose over time to a maximum of 6 capsules a day over a period of 45 to 75 days.

• Before the max dose of 6 had been reached, the IC symptoms appeared to subside at lower than 6 capsules a day and then returned. A lesson of the CTS/Boswellia experience was that the symptoms might be pressed to vanish at a higher dose.

• She took 6 capsules a day for about a month.

• A few weeks ago, due to a shipping/delivery problem, she ran out of Curcumin and didn’t have product for 10 days. She experienced no IC symptoms during that time.

• Most recently, with product back in hand, she’s taking 4 capsules a day and the current strategy is to reduce that dose by 1 capsule per week for 3 weeks. The current plan is to continue to take at least 1 capsule per day indefinitely.

• Needless to say, my friend is happy to have this multi-year condition addressed, at least for now.

Feedback especially appreciated because we know of no other comparable experiment from which we might learn. All feedback, constructive or otherwise, has the potential to add value.

Edited by wccaguy, 31 October 2014 - 11:24 PM.

[HighDesertWizard]

In my immediately previous post, I provided an overview of my friend’s attempt to address her multi-year Interstitial Cystitis (IC) disorder and symptoms. In this post, I provide the study reference links that led me to believe a high dose regimen of Super BioCurcumin from the LEF might work favorably for her.

 

1 - I took insights seriously from my personal experience with eliminating my Carpal Tunnel Syndrome symptoms with high dose Boswellia [AKBA].

 

2 - I used Google Scholar to try to find a gene associated with IC. I found this study.

 

Epigenetic reprogramming: a possible etiological factor in bladder pain syndrome/interstitial cystitis?

PURPOSE:

The etiology of bladder pain syndrome/interstitial cystitis is poorly understood. The possibility that epigenetic reprogramming may have a role is discussed.

MATERIALS AND METHODS:

A literature search was performed with the Entrez-PubMed® database using the key words urinary bladder, epigenetics, epigenetic mechanisms, interstitial cystitis, diagnosis, etiology, urothelial cells, mast cells, nerve fibers, nerves, nerve growth factor, recurrent injury, stem cells, inflammatory mediators and demethylases.

RESULTS:

The uroepithelium is intimately associated with the nervous system. Sensory input at the apical surface of umbrella cells regulates bladder function via a transmural signaling pathway. When umbrella cells are shed in response to noxious stimuli, stem cells in the basal layer become exposed. The polycomb group genes are key in the maintenance of adult stem cells. The polycomb group genes mediate gene silencing and repress transdifferentiation by methylating lysine 27 of histone H3 (H3K27me3). Jmjd3, an enzyme demethylating H3K27me3, antagonizes polycomb group genes mediated silencing. Inflammatory stimuli are strong inducers of Jmjd3 and may reverse gene silencing in stem cells, modifying the differentiation pattern. Epigenetic processes involving H3K27 methylation are multistable processes. Transient signaling, eg by lipopolysaccharide, triggers epigenetic reprogramming and establishes one of the alternative regulatory states. Once established such states can be maintained and propagated even in the absence of the initial signal.

CONCLUSIONS:

We postulate that similar epigenetic reprogramming mechanisms in the bladder may provide an explanation for uroepithelial, mast cells and nerve cell abnormalities in bladder pain syndrome/interstitial cystitis, as well as propagation of this altered state in the absence of the signal that may have triggered it. It also provides a new experimental paradigm for exploring the etiology of bladder pain syndrome/interstitial cystitis. Data supporting this hypothesis would provide a rationale for new diagnostic as well as treatment options for bladder pain syndrome/interstitial cystitis.

 

3 - I then looked for studies referencing the H3K27me3 Histone and the Jmjd3 enzyme and various anti-inflammatories. I got significantly meaningful hits with Curcumin.

 

Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells

 

Induction of apoptosis by sulforaphane and curcumin and expression profile of jmjd3, a key histone demethylase in breast cancer cell line MDA-MB-231

 

4 - There are issues with the Bioavailability of Curcumin. To my knowledge, there is no Curcumin formulation better than the LEF formulation referenced here.

 

5 - To my knowledge, there is no study showing long term toxic effects of using Curcumin at the dosing level of 6 capsules per day.

Let me be clear... I am Not At All suggesting that I've Proven my friend's IC symptoms were reduced/eliminated via an Epigenetic means. 

That said, I believe 

• I have provided Credible Evidence that her experience might best be Explained via Epigenetic means. I believe that Explanation to be as credible as any other Explanation.
• her experience provides a basis for thinking seriously about the use of Curcumin for other disorders that include the H3K27me3 Histone family. 

Looking forward to feedback.

Edited by wccaguy, 31 October 2014 - 11:46 PM.

[Avatar of Horus]

In my immediately previous post, I provided an overview of my friend’s attempt to address her multi-year Interstitial Cystitis (IC) disorder and symptoms. In this post, I provide the study reference links that led me to believe a high dose regimen of Super BioCurcumin from the LEF might work favorably for her.
 
1 - I took insights seriously from my personal experience with eliminating my Carpal Tunnel Syndrome symptoms with high dose Boswellia [AKBA].
 
2 - I used Google Scholar to try to find a gene associated with IC. I found this study.
 

Epigenetic reprogramming: a possible etiological factor in bladder pain syndrome/interstitial cystitis?

PURPOSE:

The etiology of bladder pain syndrome/interstitial cystitis is poorly understood. The possibility that epigenetic reprogramming may have a role is discussed.

...

RESULTS:

The uroepithelium is intimately associated with the nervous system. Sensory input at the apical surface of umbrella cells regulates bladder function via a transmural signaling pathway. When umbrella cells are shed in response to noxious stimuli, stem cells in the basal layer become exposed. The polycomb group genes are key in the maintenance of adult stem cells. The polycomb group genes mediate gene silencing and repress transdifferentiation by methylating lysine 27 of histone H3 (H3K27me3). Jmjd3, an enzyme demethylating H3K27me3, antagonizes polycomb group genes mediated silencing. Inflammatory stimuli are strong inducers of Jmjd3 and may reverse gene silencing in stem cells, modifying the differentiation pattern. Epigenetic processes involving H3K27 methylation are multistable processes. Transient signaling, eg by lipopolysaccharide, triggers epigenetic reprogramming and establishes one of the alternative regulatory states. Once established such states can be maintained and propagated even in the absence of the initial signal.

... 
3 - I then looked for studies referencing the H3K27me3 Histone and the Jmjd3 enzyme and various anti-inflammatories. I got significantly meaningful hits with Curcumin.
 

Epigenetic CpG demethylation of the promoter and reactivation of the expression of Neurog1 by curcumin in prostate LNCaP cells

 

Induction of apoptosis by sulforaphane and curcumin and expression profile of jmjd3, a key histone demethylase in breast cancer cell line MDA-MB-231

... 
5 - To my knowledge, there is no study showing long term toxic effects of using Curcumin at the dosing level of 6 capsules per day.

Let me be clear... I am Not At All suggesting that I've Proven my friend's IC symptoms were reduced/eliminated via an Epigenetic means. 

That said, I believe

• I have provided Credible Evidence that her experience might best be Explained via Epigenetic means. I believe that Explanation to be as credible as any other Explanation.
• her experience provides a basis for thinking seriously about the use of Curcumin for other disorders that include the H3K27me3 Histone family. 

Looking forward to feedback.

 

This
"polycomb group genes are key in the maintenance of adult stem cells. The polycomb group genes mediate gene silencing and repress transdifferentiation by methylating lysine 27 of histone H3 (H3K27me3)"
is the EZH2.
And a histone lysine demethylase pair of it is the Jumonji 3/Jmjd3 gene KDM6B.
Therefore you may possibly get some meaningful information by combining the data that you collected above with that of a previous study, this:

 

I am interested too. My current focus is the EZH2, Enhancer of Zeste homolog 2 protein, which is a histone lysine methyltransferase, but it controls the activity of the DNA methyltransferases.

Many studies have found Curcumin to trigger Epigenetic Effects, including this study note an effect on EZH2.

http://www.ncbi.nlm....pubmed/20385124

 

Because it seems that curcumin can decrease the expression of both protein, and the combined level may be of some interest.
Also in supplementation other factors/hormones may need to/should be considered, that may exert additional control over the DNA and/or histone epigenetic status, for example, the thesis of the second link you mentioned in your 3rd point cites a study:
H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERα ligand dependency
Svotelis et al. 2011 link:http://www.ncbi.nlm....pubmed/21841772
that presents such specific regulatory mechanisms: e.g. the estrogen / estrogen receptor alpha, and the epidermal growth factor receptor 2 pathways.

[HighDesertWizard]

This

"polycomb group genes are key in the maintenance of adult stem cells. The polycomb group genes mediate gene silencing and repress transdifferentiation by methylating lysine 27 of histone H3 (H3K27me3)"
is the EZH2.
And a histone lysine demethylase pair of it is the Jumonji 3/Jmjd3 gene KDM6B.
Therefore you may possibly get some meaningful information by combining the data that you collected above with that of a previous study, this:

 

I am interested too. My current focus is the EZH2, Enhancer of Zeste homolog 2 protein, which is a histone lysine methyltransferase, but it controls the activity of the DNA methyltransferases.

Many studies have found Curcumin to trigger Epigenetic Effects, including this study note an effect on EZH2.

http://www.ncbi.nlm....pubmed/20385124

 

Because it seems that curcumin can decrease the expression of both protein, and the combined level may be of some interest.
Also in supplementation other factors/hormones may need to/should be considered, that may exert additional control over the DNA and/or histone epigenetic status, for example, the thesis of the second link you mentioned in your 3rd point cites a study:
H3K27 demethylation by JMJD3 at a poised enhancer of anti-apoptotic gene BCL2 determines ERα ligand dependency
Svotelis et al. 2011 link:http://www.ncbi.nlm....pubmed/21841772
that presents such specific regulatory mechanisms: e.g. the estrogen / estrogen receptor alpha, and the epidermal growth factor receptor 2 pathways.

 

Avatar... Thanks for your post. I wasn't paying close enough attention the first time you replied. I will now. I'll work to get a handle on what you've posted and get back with questions and thoughts. Thanks!

[DorianGrey]

Here is an interesting link on a common HDACI:

http://onlinelibrary...02/mc.22224/pdf

Sulforaphane (the broccoli stuff) is downregulating HDAC. It is known to prevent cancer, and it is found in a few food sources at high levels, a few supplements in the mid-price range are also available.

 

http://www.livestron...n-sulforaphane/

Edited by DorianGrey, 29 November 2014 - 11:37 PM.

[HighDesertWizard]

 

<< snip >>

I believe I once triggered significant and positive Epigenetic change in myself by accident...

<< snip >>

 

... my early stage CTS symptoms may have vanished in a very short time via epigenetic processes through Mega Doses of 5-Loxin - Boswellia [AKBA]. In this post, I'll provide links to studies that suggest this hypothesis is not without foundation.

<< snip >>

 

<< SNIP >>

 

-------------------------------------------------

I have a mid-50s, female friend who who has suffered from Interstitial Cystitis (IC) for years. Recommended changes in diet would make a difference but have been difficult to follow consistently. And periods of stress would exacerbate the pain symptoms even when the proper diet was followed. To make a long story short, based on my own experience and research I summarize in my next post, my friend decided to do her own n=1 experiment to address her IC.

 

<< SNIP >>

 

An update on my friend's taking the Life Extension Curcumin product to rid herself of Interstitial Cystitis...

She is now taking only two capsules per day with no symptoms reappearing.. The plan is that she will drop to 2 capsules per day in the next week or two. If the symptoms do recur, she will increase the dose.

 

More updates over time...

[stefan_001]

<< snip >>
I believe I once triggered significant and positive Epigenetic change in myself by accident...
<< snip >>

 

... my early stage CTS symptoms may have vanished in a very short time via epigenetic processes through Mega Doses of 5-Loxin - Boswellia [AKBA]. In this post, I'll provide links to studies that suggest this hypothesis is not without foundation.
<< snip >>

 
<< SNIP >>
 
-------------------------------------------------
I have a mid-50s, female friend who who has suffered from Interstitial Cystitis (IC) for years. Recommended changes in diet would make a difference but have been difficult to follow consistently. And periods of stress would exacerbate the pain symptoms even when the proper diet was followed. To make a long story short, based on my own experience and research I summarize in my next post, my friend decided to do her own n=1 experiment to address her IC.
 
<< SNIP >>

 
An update on my friend's taking the Life Extension Curcumin product to rid herself of Interstitial Cystitis...
She is now taking only two capsules per day with no symptoms reappearing.. The plan is that she will drop to 2 capsules per day in the next week or two. If the symptoms do recur, she will increase the dose.
 
More updates over time...

Hello HDW, was wondering whether your friends positive path continued?
Stefan

[Multivitz]

Ok guys I know this is an old thread.

For the cancer histeria,
A cell with adiquate Silica content never gets canceous.
Cancer is the bodies natural protective response to acid metabolites.

Vitamin D3,
It gets made in to a hormone.
It interacts everywhere in the body including inside the cells.
It carries minerals.
It can control two thirds of our DNA switching (1500 pairs!)
It makes you high.
It is a major growth factor and without major food supplementation can waste the bodies supplies.
It is present in lots of foods in varying forms.
Mustrooms make the best form of D3 supplememts for long term use.
It has an anti D3 form that is produced in the body that can block it's effect on cells, I think this is only possible from excess sun exposure, if I'm wrong please correct me.
Getting to the blood stream, when formed by the UV action, can take a couple of days.
It may need to balance with other oil based vitamins, so watch for symptoms.
Supplementation can cause visual hallucinations ( especially when taken with Magnesium) like waves, don't be alarmed it's your mind loosening up!


DNA,
Is a product of it's environment, medical changes to it are,at best, forced.
The cell has filaments inside that act a channels for photons, DNA has photonic activity, fact.
A cell will function without its DNA, it's cell wall does most of the work.
Fragments of DNA float in the blood collecting photons and are harmless.

Magnesium,
You can never over alkali the body, but taking loads will ultimately dry up ones oils and phosphorus based nutrients.
It has a protective effect on cells.
Nerve fibres are made of it!
Chlorophyll is blood protein, but with Magnesium instead of Iron (iron gets recycled by the liver)
The third eye produces many substances that effect other glands, Magnesium is a part of DMT, Serotonin, these molecules are extremely simular. Salmonella poisoning has the same symptoms as Serotonin poisoning! Most Serotonin is managed in the intestines as an immune agent and for muscle action.
Magnesium pairs with Potassium(and other substances) to create an oxygen carrying molecule that can permeate tissues blood cells can't reach.
It is the lightest Metallic element.
It is involved in transmutation(very important). The roles minerals play in the body are not fully understood by mainstream science, don't be fooled by it's claims.
Silica normalises Magnesium and other minerals in blood serum levels.
The Magnesium Miracle, is a good book and may tell you more.
Long term Magnesium use will cause a Zinc deficiency(most people are deficient in Zinc) Molybdenum also has trouble and is totally essential for health.

I can personally say D3 will restore the DNA, but a careful diet with adiquate nutrients has to be available for the effects to work. Eating rice alone works well for a start. Living on fresh air is only possible when the body has all it's elements and hydration is maintained to a degree and NOT over done.