115 replies to this topic

[Hedrock]

P.S.

By the way - Did you know Resveratrol is also a HDAC1-Inhibitor? (indirectly)

So do EGCG and Resvertrol reprogram you and how efficient is this?

Article about Resveratrol and Epigenetics


--> Ok to EGCG and RESV!!! I take both supplements anyway, but now I begin to understand the way they work.

Edited by Hedrock, 18 April 2010 - 07:46 PM.

[N.T.M.]

P.S.

By the way - Did you know Resveratrol is also a HDAC1-Inhibitor? (indirectly)

So do EGCG and Resvertrol reprogram you and how efficient is this?

Article about Resveratrol and Epigenetics


--> Ok to EGCG and RESV!!! I take both supplements anyway, but now I begin to understand the way they work.

I read this and thought you might find it interesting:

"There is no law of
nature to prevent us from instructing the cells of an adult
human being to avoid aging by, for example, changing the
genetic program at a DNA or epigenetic level. Since, like any
disease, aging results from disrupted or unbalanced molecules
it is also theoretically possible to reverse age-related changes
by precise molecular and cellular therapies."

-João Pedro de Magalhães, Ph.D.

[Hedrock]

Hi N.T.M.,

thanks, I also have found something for you:

The progression of methylation with aging:

Picture

Maybe this could change your point of view on the importance of methylation.

The whole article seems very interesting.

Of course aging has many aspects and I never supported a one-reason-aging-theory. Aging is a multifactorial process, but methylation and differentiation play a enormous role.

BR

Hedrock

[AgeVivo]

i) does anybody have one clear example of methylation *causing* age-related troubles?
ii) does anybody see one clear approach to change methylation in a beneficial way?

I'm asking the question because I did not see such things in the above post, and there are many things that change with age (such as water concentration of the body) but it doesn't mean that i) they participate in the ageing deterioration ii) they lead us to some anti-ageing discoveries.

[N.T.M.]

Hi N.T.M.,

thanks, I also have found something for you:

The progression of methylation with aging:

Picture

Maybe this could change your point of view on the importance of methylation.

The whole article seems very interesting.

Of course aging has many aspects and I never supported a one-reason-aging-theory. Aging is a multifactorial process, but methylation and differentiation play a enormous role.

BR

Hedrock

Looks very interesting. I'm gonna go through it and read it all.

Also, I'd like to recant my comments regarding the inconsequentiality of telomere length within current life spans. It seems that it just being short affects an organism deleteriously. Luckily though, there's already a therapy to renew them.

[Luna]

Hi N.T.M.,

thanks, I also have found something for you:

The progression of methylation with aging:

Picture

Maybe this could change your point of view on the importance of methylation.

The whole article seems very interesting.

Of course aging has many aspects and I never supported a one-reason-aging-theory. Aging is a multifactorial process, but methylation and differentiation play a enormous role.

BR

Hedrock

Looks very interesting. I'm gonna go through it and read it all.

Also, I'd like to recant my comments regarding the inconsequentiality of telomere length within current life spans. It seems that it just being short affects an organism deleteriously. Luckily though, there's already a therapy to renew them.

Is it a therapy that is available for just anyone? how do you do that? what about the risk for cancer?

[Hedrock]

Is it a therapy that is available for just anyone? how do you do that? what about the risk for cancer?

Do you mean telomere therapy or stem cell therapy or full epigenetic therapy by epigenetic reprogramming?

See the difference:

1.) Telomere therapy only lengthens the telomeres. The telonmeres are important, yes! Maybe you would live longer but your phenotype would not change to be young again. With 120 you would look like 80 still. But you would never look like 20 again.

2.) Stem cell therapy would make some renewal but not complete. You would look younger but it is a slow change and it would be very difficult to completely reverse aging.

3.) Epigenetic reprogramming means - full renewal. Go back to the point you like. You are 80 look like 80 and 2 months later after epigenetic therapy you look like 20 again and feel like 20. This is the most powerful way.


Ummm, risk of cancer is high!

Edited by Hedrock, 30 April 2010 - 06:42 PM.

[N.T.M.]

Hi N.T.M.,

thanks, I also have found something for you:

The progression of methylation with aging:

Picture

Maybe this could change your point of view on the importance of methylation.

The whole article seems very interesting.

Of course aging has many aspects and I never supported a one-reason-aging-theory. Aging is a multifactorial process, but methylation and differentiation play a enormous role.

BR

Hedrock

Looks very interesting. I'm gonna go through it and read it all.

Also, I'd like to recant my comments regarding the inconsequentiality of telomere length within current life spans. It seems that it just being short affects an organism deleteriously. Luckily though, there's already a therapy to renew them.

Is it a therapy that is available for just anyone? how do you do that? what about the risk for cancer?

Yes, for anyone.

I just wrote a blog about it actually:

http://blightofdeath...cumventing.html

Regarding cancer risk:

One of the prerequisites for a cancerous cell to take hold is to posses a mutation which quickly relengthens telomeres (obviously via telomerase). Without that the potential malignancy would quickly exhaust its allotted replications and form nothing more than a small benign tumor.

Renewing telomeres via TA-65 would not elongate them fast enough to support the proliferation which cancer undergoes. Besides, the primary defense against cancer (debatably) is apoptosis. Unless this mechanism is impeded, neighboring cells should be able to induce this on any cells exhibiting any instability. In fact it'd make sense to reason that (ironically) the pathology associated with short telomeres may contribute to this inhibition.

Is it a therapy that is available for just anyone? how do you do that? what about the risk for cancer?

Do you mean telomere therapy or stem cell therapy or full epigenetic therapy by epigenetic reprogramming?

See the difference:

1.) Telomere therapy only lengthens the telomeres. The telonmeres are important, yes! Maybe you would live longer but your phenotype would not change to be young again. With 120 you would look like 80 still. But you would never look like 20 again.

2.) Stem cell therapy would make some renewal but not complete. You would look younger but it is a slow change and it would be very difficult to completely reverse aging.

3.) Epigenetic reprogramming means - full renewal. Go back to the point you like. You are 80 look like 80 and 2 months later after epigenetic therapy you look like 20 again and feel like 20. This is the most powerful way.


Ummm, risk of cancer is high!

An understandable caveat, but as I said, I disagree.

*edit* Yes, telomere length is only one aspect (a very important one though). It alone may confer several decades of extended life.

3.) Epigenetic reprogramming means - full renewal. Go back to the point you like. You are 80 look like 80 and 2 months later after epigenetic therapy you look like 20 again and feel like 20. This is the most powerful way.

It would not be full age reversal. AGEs would still impair repair mechanisms, beta amyloid in the brain, etc.

Granted it is a part, but only a part.

Edited by N.T.M., 01 May 2010 - 09:12 AM.

[Hedrock]

3.) Epigenetic reprogramming means - full renewal. Go back to the point you like. You are 80 look like 80 and 2 months later after epigenetic therapy you look like 20 again and feel like 20. This is the most powerful way.

It would not be full age reversal. AGEs would still impair repair mechanisms, beta amyloid in the brain, etc.

Granted it is a part, but only a part.

Epigenetics would reverse phenotype completely. Even AGEs are eliminated by this way.

The cell simply would produce new proteins and remove the old (glycated) proteins.

Yes, AGE have a role in aging and diminishing them would help. But the body itself has the mechanisms to eliminate AGE by autophagy, cell division and an intact immune system. These mechanisms are increased by reprogramming.

*edit* Yes, telomere length is only one aspect (a very important one though). It alone may confer several decades of extended life.

Agreed!

Immortality is impossible without telomere lengthening.

Renewing telomeres via TA-65 would not elongate them fast enough to support the proliferation which cancer undergoes. Besides, the primary defense against cancer (debatably) is apoptosis. Unless this mechanism is impeded, neighboring cells should be able to induce this on any cells exhibiting any instability. In fact it'd make sense to reason that (ironically) the pathology associated with short telomeres may contribute to this inhibition.

It seems to be a safe way, but we actually don't know much about long term effects!

I also support cycloastogenol and astragaloside IV. But there is still not too much evidence yet.

The problem is: Telomerase would lengthen life, but it would not reactivate silenced genes, the phenotype aging. The reversal of phenotype aging is not only important for a good look. It is important for preventing heart diseases, reactivating liver processes, strenghening immune system. What is the sense of having long telomeres if you die of a heart attack? If you die of a catarrh?

Epigenetic reprogramming is not just an option. It is a must!

The telomere lengthening therapy & the epigenetic reprogramming therapy must work together!

[Hedrock]

i) does anybody have one clear example of methylation *causing* age-related troubles?

Read this:

Epigenetics of aging

Epigenetics of aging: Free at google-books

Epigenetics and the Aging Process . . . . . . . . . . . . . . . . . . . . . 1
Trygve O. Tollefsbol
Part I DNA Methylation and Histone Modifications in Aging
Age-Related Genomic Hypomethylation . . . . . . . . . . . . . . . . . . 11
Igor P. Pogribny and Boris F. Vanyushin
Gene-Specific Hypermethylation in Aging . . . . . . . . . . . . . . . . . 29
Adebayo D. Akintola and Alan R. Parrish
Aging and Non-sirtuin Histone Modifications . . . . . . . . . . . . . . . 41
Inga Kadish
Sirtuins and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Yuqing Dong and Sige Zou
Chromatin in Senescent Cells: A Conduit for the Anti-Aging
Effects of Wnt Signaling? . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Gowrishankar Banumathy and Peter D. Adams
S-Adenosylmethionine: Simple Agent of Methylation and Secret
to Aging and Metabolism? . . . . . . . . . . . . . . . . . . . . . . . . . 107
Wil A.M. Loenen
Part II Other Epigenetic Processes and Aging
Polycomb Group of Genes and the Epigenetics of Aging . . . . . . . . . 135
Krishnaveni Mishra and Rakesh K. Mishra
Chromosomal Position Effect and Aging . . . . . . . . . . . . . . . . . . 151
Eric Gilson and Frédérique Magdinier
Noncoding RNA for Presymptomatic Diagnosis
of Age-Dependent Disease . . . . . . . . . . . . . . . . . . . . . . . . . . 177
Eugenia Wang
vii
viii Contents
Part III Impact of Epigenetics on Aging
Telomerase Control by Epigenetic Processes in Cellular Senescence . . 191
Huaping Chen and Trygve O. Tollefsbol
Telomeres, Epigenetics, and Aging . . . . . . . . . . . . . . . . . . . . . 205
J. Arturo Londoño-Vallejo
Contributions of Tumor Suppressors to the Epigenetic
Regulation of Aging Cells . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Pinaki Bose, Amudha Ganapathy, and Karl Riabowol
Epigenetic Drift and Aging . . . . . . . . . . . . . . . . . . . . . . . . . 257
Ester Lara, Vincenzo Calvanese, and Mario F. Fraga
Role of Epigenetics in Age-Related Long-Term Memory Loss . . . . . . 275
J. Tyson DeAngelis and Trygve O. Tollefsbol
Part IV Epigenetics of Age-Related Diseases
The Epigenetics of Age-Related Cancers . . . . . . . . . . . . . . . . . . 285
Kristen H. Taylor, Lynda B. Bennett, Gerald L. Arthur,
Huidong Shi,
and Charles W. Caldwell
DNA Methylation and Alzheimer’s Disease . . . . . . . . . . . . . . . . 315
Thomas van Groen
DNA Methylation, Age-Related Immune Defects, and Autoimmunity . . 327
Jörg J. Goronzy, Guangjin Li, and Cornelia M. Weyand
Epigenetic Silencing of Progeroid Syndromes . . . . . . . . . . . . . . . 345
Ruben Agrelo
DNA Methylation and Osteoarthritis . . . . . . . . . . . . . . . . . . . . 371
Helmtrud I. Roach
Part V Epigenetic Interventions and Aging
Histone-Modifying Drugs in Aging . . . . . . . . . . . . . . . . . . . . . 395
Ulrich Mahlknecht and Barbara Zschoernig
Dietary Effect on Epigenetics During the Aging Process . . . . . . . . . 407
Yuanyuan Li and Trygve O. Tollefsbol
Environmental Effects on Age-Associated Epigenetics . . . . . . . . . . 417
Sabita N. Saldanha, Ashley McCollum, and Trygve O. Tollefsbol
Part VI Future Directions/Perspectives
Future Directions in Research on the Epigenetics of Aging . . . . . . . . 433
Huidong Shi and Charles W. Caldwell
Contents ix
Perspectives in Aging and Epigenetics . . . . . . . . . . . . . . . . . . . 447
Robin Holliday
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457

ii) does anybody see one clear approach to change methylation in a beneficial way?

Yes I do have one. But the problem is, I'm not sure if it is too risky.

[AgeVivo]

Thank you Hedrock!
- I understand that with aging there is general hypomethylation and local hyper methylation. Would you advise a specific paragraph in the book that shows/says that such methylation changes acually *cause* are-related troubles? (in general; not some specific premature-ageing disease). We should quote it here, it would make the point.
- What is the approach you are thinking of?

[bacopa]

This threads gets more and more interesting.

I would love to hear more about the herbs you take and in what quantity? How do you prepare them?

Is it ok to post just the substances I take, which I identified to have epigenetic potential? The quantities I will post another day in my regimen in the other subforum.

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

Ginseng, purified Ginsenosides, Reishi, Gotu Kola, Polygonum multiflorum (Resveratrol), Ashwaghanda, Sibirian ginseng, Jiaogulan, Fenugreek, Astragalosides, Silibinin (Silymarin), 20-Hydroxyecdysone, Turkesterone, Makisterone, Inokosterones, Cyasterones, Genistein, Daidzein, Glycitein, EGCG, Melatonin, Diosgenine, 7-keto-DHEA, Magnolol, Honokiol, Parthenolide.


Sorry, it sounds like a standard regimen!

Most people do not know of the epigenetic potential of their supplements (might have just a small effect, but who knows!?)

I don't want to talk about the substances here. Just show that we all are already using epigenetics on our way!

Everybody who takes just one of these substances is already working at his change of epigenetics!


P.S. Edit: Vitamine D3 also has!

some of those supplements you mentioned do NOT sound like a standard regimen!

[Hedrock]

Thank you Hedrock!
- I understand that with aging there is general hypomethylation and local hyper methylation.

Ok, you are right. But this does not mean that the main danger comes from the hypomethylation.

Would you advise a specific paragraph in the book that shows/says that such methylation changes acually *cause* are-related troubles? (in general; not some specific premature-ageing disease).

The aging troubles are caused at about 90 percent by the local hypermethylation and the changed pattern. Hypomethylation may lead to cancer too in maybe 10%, but it needs inactivated tumor suppressors for this. (edit: I just mean the relation of hypermethylation and hypomethylation. Of course there are many other reasons for age-related troubles!)

Hypomethylation is more the symptom of aging than the reason.

Here the proof:

Look in the linked source in the chapter 4.1 - 4.4

Example:

Recently, vascular disease, another typical age-related disease, was shown to be associated with promoter hypermethylation of the estrogen receptors (ER ) and (ER ). There was a significant increase in hypermethylation of ER and ER in coronary atherosclerotic plaques [122,123].

- What is the approach you are thinking of?

At the moment I tend more to the demethylation / remethylation mechanism. I think I can control the cancer risk and the SLE-risk now.

I don't know if it is good to go into the details at the moment.

Just so far:
1.) Demethylation by DNMT1-inhibitors and histone acetylation by HDAC-inhibitors
2.) Remethylation by hormones and hormone-like substances
3.) Addition of special cancer / SLE inhibitors

Edited by Hedrock, 01 May 2010 - 05:55 PM.

[VidX]

Some interesting read: http://anti-agingfir...na-methylation/

[AgeVivo]

Look in the linked source in the chapter 4.1 - 4.4

Example:

Recently, vascular disease, another typical age-related disease, was shown to be associated with promoter hypermethylation of the estrogen receptors (ER ) and (ER ). There was a significant increase in hypermethylation of ER and ER in coronary atherosclerotic plaques [122,123].

Looking at the references (123 for example, http://pubmed.org/10727665) it does not say that it is a cause of the pathology. Atherosclerosis is a complex process and one may find some association with pretty much any pathway/theory of aging one is looking for -- that's different from causality. Methylation changes *may* be key in ageing but it needs to be shown, typically by acting on methylation to produce improvements and doublechecking that it requires that methylation action.

- What is the approach you are thinking of?

At the moment I tend more to the demethylation / remethylation mechanism. I think I can control the cancer risk and the SLE-risk now.

I don't know if it is good to go into the details at the moment.

Just so far:
1.) Demethylation by DNMT1-inhibitors and histone acetylation by HDAC-inhibitors
2.) Remethylation by hormones and hormone-like substances
3.) Addition of special cancer / SLE inhibitors

Are you working in a lab? Would you be aware of a simple system (plant, red fish, other) to test it, perhaps even at home (even if one has to take care as obviously demethylation/remethylation compounds can be toxic)? I'd be interested.

[N.T.M.]

3.) Epigenetic reprogramming means - full renewal. Go back to the point you like. You are 80 look like 80 and 2 months later after epigenetic therapy you look like 20 again and feel like 20. This is the most powerful way.

It would not be full age reversal. AGEs would still impair repair mechanisms, beta amyloid in the brain, etc.

Granted it is a part, but only a part.

Epigenetics would reverse phenotype completely. Even AGEs are eliminated by this way.

The cell simply would produce new proteins and remove the old (glycated) proteins.

Yes, AGE have a role in aging and diminishing them would help. But the body itself has the mechanisms to eliminate AGE by autophagy, cell division and an intact immune system. These mechanisms are increased by reprogramming.

I'm really not sure that's feasible. I've never read anything about the body degrading AGEs.

Any evidence to substantiate this?

IMO AGE-breaking drugs are the only way.

[Hedrock]

Some interesting read: http://anti-agingfir...na-methylation/

Interesting! Thank you!

I also read the blog of Vince Giulano and to my opinion he is one of the most brilliant minds in our scene.

Some of my ideas I have from his blog.

[Hedrock]

Looking at the references (123 for example, http://pubmed.org/10727665) it does not say that it is a cause of the pathology. Atherosclerosis is a complex process and one may find some association with pretty much any pathway/theory of aging one is looking for -- that's different from causality. Methylation changes *may* be key in ageing but it needs to be shown, typically by acting on methylation to produce improvements and doublechecking that it requires that methylation action.

You are right. We are moving in a high speculative area. New territory,

Interesting that the high appeciated Resveratrol and EGCG are both epigenetic supplements. Resveratrol (HDAC-Inhibitor) affects more the acetylation while EGCG (DNMT1-Inhibitor) does the demethylation. There are so many studies about Resveratrol and EGCG. The studies about them lead me to some conclusions. Don't know if it is scientific acceptable to draw these consequences but it is the only possibility I have,

The other option would be to wait till science is ready. But I do not have enough time for waiting.

Resveratrol and EGCG are good, but actually we would need something stronger to reprogram cells. Or a special boosting combination. This is the way I'm thinking about at the moment.

There are so many scientific studies that is is difficult to see the coherence.

Are you working in a lab? Would you be aware of a simple system (plant, red fish, other) to test it, perhaps even at home (even if one has to take care as obviously demethylation/remethylation compounds can be toxic)? I'd be interested.

No, I do not work in a lab.

Only mental work at the moment.


Edit: Correction. When I went through my appartment today I saw it IS A LABORATORY, All full with chemical substances, but where is the guinea pig? Is it me? O my god,what am I doing?

Edited by Hedrock, 02 May 2010 - 09:46 AM.

[Hedrock]

Hypothesis 1: Synergism of different epigenetic mechanisms increases DNA methylation reprogramming

Epigenetics involves different mechanisms. Methylation is only one. If we change several mechanisms at the same time, reprogramming would be more efficient.

Although histone modifications occur throughout the entire sequence, the unstructured N-termini of histones (called histone tails) are particularly highly modified. These modifications include acetylation, methylation, ubiquitylation, phosphorylation and sumoylation.

Source: wiki

If we take a simple supplemental approach. The substances are well known supplements:

(De-)Methylation: EGCG
Acetylation: Resveratrol
(De-)Phosphorylation: Honokiol/magnolol (to understand the action of honkiol read this)
Ubiquitylation: ??? To be defined
Sumoylation: ??? To be defined

So in my theory Resveratrol and EGCG together would have some synergistic action, more than the sum of the single actions. All 3 substances EGCG, Resveratrol and Honokiol should be more synergistic.

It is only theory to be proved. It is not an advice! Maybe I'm wrong.

But if I'm true this would be a great progress, cause we understand how to combine the epigenetic actions.

What do you think about it?

[VidX]

Interesting! Thank you!
I also read the blog of Vince Giulano and to my opinion he is one of the most brilliant minds in our scene.
Some of my ideas I have from his blog.

Yeah, Vince is an impressive person.

BTW - what are your thoughts on a possible gene damage, that's mentioned in that text, as a consequence o f an epigenic activity? I mean - in that case we'd need some gene therapy to repair the damaged ones (as a "young" methylation pattern can't work on a "good" gene, that has been damaged in some way, to fully restore young phenotype).

[treonsverdery]

well it might be the thing that the worlds gentlest methylation reagent would be the thing yet you would have to get that to the DNA

an approach that may be used to methylate actively transcribed DNA is to modify enzymes like topoisomerase to methylate as the go their repairative way Actually numerous of the DNA repair enzymes could be modified to cause methylation as they traverse DNA

this is a link http://www.faqs.org/...app/20090241226 to a commercial enzyme that methylates perhaps a hybrid of the described gene sequences with those of DNA repair enzymes plus a promotor switch could be made part of a creature then variations on the amount of actual methylation at repair sityes could be measured as effecting longevity

Edited by treonsverdery, 04 May 2010 - 12:49 AM.

[urba]

The telomere lengthening therapy & the epigenetic reprogramming therapy must work together!

Thank You, Hedrock for the all Your ideas!
This is very interesting summary -

Oncogene (2010) 29, 1561–1565; doi:10.1038/onc.2010.15
2009 Nobel Prize in Physiology or Medicine: telomeres and telomerase

E Varela1 and M A Blasco1

http://www.nature.co.../onc201015a.htm


and usefull experiment -

DNA methylation is a common event in gastric carcinogenesis. hTERT seems to be the rate-limiting determinant of telomerase activation, which is responsible for stability and life span. hTERT hypermethylation has been associated with telomerase expression. In the present study...

from Biomarkers. 2009 Dec;14(8):630-6

article abstract

What about the target DNA methylation control?

[Hedrock]

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,

Edited by Hedrock, 08 May 2010 - 10:06 AM.

[Hedrock]

Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system

Yes, if the estrogen receptor is methylated, this will lead to aging.

Demethylation of the estrogen receptor would enable body mechanism of DNA methylation reprogramming.

Of course it are the CpG islands again which are hypermethylated.

It is well established that a major mechanism for down regulation of gene expression is methylation of a cytosine and guanine rich area in the promoter region of the gene, called a CpG island. This promoter associated CpG island methylation has consistently been associated with permanent inactivation of gene transcription [12] in multiple systems. For example, this process is physiologically involved in inactivation of the X-chromosome [13] in which promoter methylation is essential to maintaining the silenced state, and where demethylation results in renewed gene expression. Promoter methylation is involved in genomic imprinting [14] in which the silenced state of the affected allele is determined by methylation of the promoter region for numerous imprinted genes, and demethylation results in bi-allelic gene expression. In addition, abnormal methylation of the promoter area of many genes appears to be an important feature of human neoplasia. Recently, CpG island methylation has been shown to be an alternative mechanism to mutation for inactivating tumor-suppressor genes [15], such as the Rb gene in retinoblastoma [16], the VHL gene in renal tumors [17] and the p16 gene in many neoplasms [18].

[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,

Thanks. this new information for me seems to be interesting and great. I've found -
In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.[62][63][64][65][66][67] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties..[40][68][69]
Honokiol has shown pro-apoptotic effects in melanoma, sarcoma, myeloma, leukemia, bladder, lung, prostate, and colon cancer cell lines.[1][2][3][4] Honokiol inhibits phosphorylation of Akt, p44/42 mitogen-activated protein kinase (MAPK), and src. Additionally, honokiol modulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and MCL1, all significant pro-angiogenic and survival factors. Honokiol induces caspase-dependent apoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects of doxorubicin and other etoposides. So potent is honokiol's pro-apoptotic effects that it overcomes even notoriously drug resistant neoplasms such as multiple myeloma and chronic B-cell leukemia.
There is increasing evidence to show that EGCG, along with other flavonoids, can be beneficial in treating brain,[8] prostate,[9][10] cervical[11] and bladder[12] cancers. EGCG has been shown to bind and inhibit the anti-apoptotic protein Bcl-xl[13] which has been implicated in both cancer cell and normal cell survival.[14] What's Your opinion?

The problem, I see, is that such great mixture You proposed would affect total 24 thousand genes (and not only them) possibly demethylating sleeping oncogenes too ref.. So, some additional tools are needed to keep oncogenes locked.

[Hedrock]

Thanks. this new information for me seems to be interesting and great. I've found -
In some lineages of cancer cell culture, resveratrol has been shown to induce apoptosis, which means it kills cells and may kill cancer cells.[62][63][64][65][66][67] Resveratrol has been shown to induce Fas/Fas ligand mediated apoptosis, p53 and cyclins A, B1 and cyclin-dependent kinases cdk 1 and 2. Resveratrol also possesses antioxidant and anti-angiogenic properties..[40][68][69]
Honokiol has shown pro-apoptotic effects in melanoma, sarcoma, myeloma, leukemia, bladder, lung, prostate, and colon cancer cell lines.[1][2][3][4] Honokiol inhibits phosphorylation of Akt, p44/42 mitogen-activated protein kinase (MAPK), and src. Additionally, honokiol modulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular endothelial growth factor (VEGF), cyclooxygenase 2 (COX-2), and MCL1, all significant pro-angiogenic and survival factors. Honokiol induces caspase-dependent apoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects of doxorubicin and other etoposides. So potent is honokiol's pro-apoptotic effects that it overcomes even notoriously drug resistant neoplasms such as multiple myeloma and chronic B-cell leukemia.
There is increasing evidence to show that EGCG, along with other flavonoids, can be beneficial in treating brain,[8] prostate,[9][10] cervical[11] and bladder[12] cancers. EGCG has been shown to bind and inhibit the anti-apoptotic protein Bcl-xl[13] which has been implicated in both cancer cell and normal cell survival.[14] What's Your opinion?

Excellent summary!

The anti-cancer activity of the 3 master substances is only one effect resulting from the regeneration of normal cell abilities. Theses substances are not only anti-cancer supplements. They are much more. Epigenetic activators.

I'm very confident in these 3 because of the cited effects.

The problem, I see, is that such great mixture You proposed would affect total 24 thousand genes (and not only them) possibly demethylating sleeping oncogenes too ref.. So, some additional tools are needed to keep oncogenes locked.

This is theoretically true. The oncogenes are a problem in theory. So I'm a bit afraid as a practical user.

But I never heared one of the 3 master substances (Resveratrol, EGCG, honokiol) leaded to cancer. Quite the contrary! These substances are well known to inhibit cancer.

Show me one study, that resveratrol, EGCG or honokiol would lead to cancer. I can show you thousands of studies they would inhibit all kinds of cancer.


Maybe the anti-Cancer and anti-promotion properties are stronger than the oncogenic activities!?

I already take all of them in large amounts. So what to do now? Stop them abruptely? Stopping now would be maybe more dangerous than to continue.

[JLL]

This is a very interesting thread. I will have to do some reading and try to learn more about this.

[urba]

This is theoretically true. The oncogenes are a problem in theory. So I'm a bit afraid as a practical user.

But I never heared one of the 3 master substances (Resveratrol, EGCG, honokiol) leaded to cancer. Quite the contrary! These substances are well known to inhibit cancer.

Show me one study, that resveratrol, EGCG or honokiol would lead to cancer. I can show you thousands of studies they would inhibit all kinds of cancer.


Maybe the anti-Cancer and anti-promotion properties are stronger than the oncogenic activities!?

I already take all of them in large amounts. So what to do now? Stop them abruptely? Stopping now would be maybe more dangerous than to continue.

It is impossible to give exact scientific answer now, but I hope propbability of cancer using Your mixture in non extreme amounts is neglible, but I'm going to study this interesting aproach You proposed more deep - it's attractive. I'm mathematician solving cancer theory problems and Your ideas give the new sightseeing of the problem too. Thanks. The other problem I could see, it is the mathematical (formal) meaming of the term REPROGRAMMING. First, we know that with aging methylation level increases, so this gives the idea to stop it or return it to the "younger state". This task is only one step of REPROGRAMING problem, but even here it is difficult imagine all full machinery of possible demethylation. First idea is make lower methylation substrate CH₃ level. It depends on all long chain of so called One carbon units reaction network involving Amino acids Serine, Methionine intake, vitamines - Folate and B₁₂ and finishing at SAM forming which participate in lots of methylation reactions - DNA methylation using DMT's is only the one. So, lot's of side physiological effects would turn on, but if someone will keep OCU flux at lowest normal level human needs it is possible to expect some DNA methylation sustain.
REPROGRAMING IDEA is much more wide and we need to define it more exactly.

[Hedrock]

I'm mathematician solving cancer theory problems and Your ideas give the new sightseeing of the problem too. Thanks. The other problem I could see, it is the mathematical (formal) meaming of the term REPROGRAMMING. First, we know that with aging methylation level increases, so this gives the idea to stop it or return it to the "younger state".

The pattern is lost anyway. Just imagine copying a sheet of printed paper. Then make the copy of the copy. The pattern is going weaker and weaker.

It doesn't matter if you take more ink or less. You will loose information anyway. That's what aging is. Loss of information.

This task is only one step of REPROGRAMING problem, but even here it is difficult imagine all full machinery of possible demethylation. First idea is make lower methylation substrate CH₃ level. It depends on all long chain of so called One carbon units reaction network involving Amino acids Serine, Methionine intake, vitamines - Folate and B₁₂ and finishing at SAM forming which participate in lots of methylation reactions - DNA methylation using DMT's is only the one. So, lot's of side physiological effects would turn on, but if someone will keep OCU flux at lowest normal level human needs it is possible to expect some DNA methylation sustain.
REPROGRAMING IDEA is much more wide and we need to define it more exactly.

The REPROGRAMING IDEA means: The body is able to reprogram itself. Not you do the reprogramming, but the body does itself UNDER SPECIAL CONDITIONS. Just generate these necessary conditions and the body will be able to reprogram completely.

The body starts with one unmethylated cell. Demethylation is the precondition. The methylation patterns are set by the cell itself. All methylation patterns are in you but only expressed once, when you are a fetus!

Compare the cell to a modern computer with windows installed. If windows is fresh installed it is running fast. Then later it is getting slower and slower and you get sometimes a bluescreen, because on your hard disk some information is lost.

So, if your windows is going to be more and more defect, the only solution is: Take the original CD with the software (or the backup CD) and reinstall the windows again. (In the comparison to the cell the starter sequences are already in the core!)

That is what I mean with reprogramming.

Of course I don't want to go back completely to the start but just to some intermediate state. This means partially demethylation and immediate remethylation by selected hormones.

Edited by Hedrock, 08 May 2010 - 05:06 PM.

[Hedrock]

This is the program in a normal live:

1.) Before Birth:

conception - estrogens from mother - programming sequence (methylation) - DHEA (+ estrogen or testosteron) from the fetus itself - programming sequence (methylation) - birth

2.) After birth

birth - melatonin - programming sequence (methylation) - DHEA - programming sequence (methylation) - estrogens/testosterone - programming sequence (methylation) - age 20 --> aging - loss in hormones / loss in methylation patterns

After 20 no programming happens any more.

Here the pictures for the DHEA

And here the pictures for the melatonin


Reverse Aging:

To my opinion the reverse hormone sequence would be the best! We should probably start with the DHEA (or 7-keto-DHEA is testo is not to be increased).

- Demethylation - DHEA - reprogramming sequence

- Demethylation - melatonin - reprogramming sequence

.... and so on

Edited by Hedrock, 08 May 2010 - 05:33 PM.