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Anybody interested in DNA Methylation Reprogramming


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#61 urba

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Posted 08 May 2010 - 05:44 PM

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.

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.

OK - interesting scetch. That's what aging is. Loss of information....... It's true. First or paralelly - loosing or gaining the structure, too. Information, too. Ageing - state of body, cells...when compared this some time before. What about methylation?
Scholars stressed - The researchers tested more than 1,500 potential DNA methylation sites from 371 genes in 14 human embryonic stem cells lines derived in several different labs and raised for different times in culture. Many of these genes, such as tumor suppressors, were cancer-related.

The human embryonic stem cells shared essentially identical methylation patterns in 49 methylation sites from 40 genes. The patterns were easily distinguishable from those present in four somatic stem cell lines, 25 cancer lines, four normal tissue lines, and four B cell lines. "Others among the 371 [stem cell genes] were also very similar," Barker said.

The researchers did report some differences in methylation patterns between the human embryonic stem cell lines, although these proved slight compared to the differences between the embryonic stem cells and other cell types.

Read more: Distinct methylation in stem cell DNA - The Scientist - Magazine of the Life Sciences[url="http://"%20<a%20href="http://www.the-scientist.com/news/display/24262/#ixzz0nMQZ1KAr""%20target="_blank">http://www.the-scien...ay/...0nMQZ1KAr"</a>"]ref[/url]
The key Reprograming target are the stem cells becouse they reborn all the rest cells dyring the year. So, when they are loosing methylation pattern they create "older" cells.

#62 urba

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Posted 08 May 2010 - 05:46 PM

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.

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.

OK - interesting scetch. That's what aging is. Loss of information....... It's true. First or paralelly - loosing or gaining the structure, too. Information, too. Ageing - state of body, cells...when compared this some time before. What about methylation?
Scholars stressed - The researchers tested more than 1,500 potential DNA methylation sites from 371 genes in 14 human embryonic stem cells lines derived in several different labs and raised for different times in culture. Many of these genes, such as tumor suppressors, were cancer-related.

The human embryonic stem cells shared essentially identical methylation patterns in 49 methylation sites from 40 genes. The patterns were easily distinguishable from those present in four somatic stem cell lines, 25 cancer lines, four normal tissue lines, and four B cell lines. "Others among the 371 [stem cell genes] were also very similar," Barker said.

The researchers did report some differences in methylation patterns between the human embryonic stem cell lines, although these proved slight compared to the differences between the embryonic stem cells and other cell types.


Read more: Distinct methylation in stem cell DNA - The Scientist - Magazine of the Life Sciences[url="http://"%20&lt;a%20href="http://www.the-scientist.com/news/display/24262/#ixzz0nMQZ1KAr""%20target="_blank"&gt;http://www.the-scien...ay/...0nMQZ1KAr"&lt;/a&gt;"]ref[/url]
The key Reprograming target are the stem cells becouse they reborn all the rest cells during the year. So, when they are loosing methylation pattern they create "older" cells.


Edited by urba, 08 May 2010 - 05:48 PM.


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#63 Hedrock

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Posted 08 May 2010 - 07:47 PM

Unexpectedly the estrogen-AID-pathway is one of the most oncogenic!

Under normal methylation conditions estrogen is not high oncogenic, else most woman would get cancer. But this is not the case.

But this situation changes dramatically when the cell core is undermethylated! The estrogen-induced AID plays an important role with the oncogenes.

Estrogen in the undermethylated cell leads to both:
1.) Oncogenic process of getting cancer - evidence for this ...... and here

Furthermore, hyperactivation of AID outside the immune system leads to oncogenesis.


2.) DNA methylation reprogramming by AID-Oct4 - evidence for this

Estrogen is a double-edged sword!

So actually not the undermethylation is the reason for coming at cancer but the estrogen (or maybe testostorone in case of prostate!).

If you are a man you could inhibit estrogen generation by high doses of zinc (aromatase inhibition).

If you are a woman you shouldn't do the reprogramming until further scientific research could exclude the risks.

The DHEA-reprogramming pathway or the melatonin-reprogramming pathway should be the better choice for the next time.

Avoid in any case the estrogen-reprogramming pathway: It is the fastest way of coming at cancer!


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.



So this might be the answer to the question how to lock oncogens! Avoiding estrogen via aromatase inhibition should be very effective.

Edited by Hedrock, 08 May 2010 - 07:59 PM.


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#64 Jay

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Posted 09 May 2010 - 02:11 AM

It is a fascinating topic indeed.

Is resveratrol a better HDAC-Inhibitor than sulforaphane? This study looked at soy, EGCG, and sulforaphane.

Edited by Jay, 09 May 2010 - 02:17 AM.


#65 urba

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Posted 09 May 2010 - 03:56 AM

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.


The REPROGRAMMING 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.


Thanks one more time! The circle of problems we touched rises immediately becouse the system we investigate is unrealy wide and complex. this is only one - biochemical, not the biological and social level - ref. So for better understanding we must be not in a great hurry. We are trying to explain how we understand some basic terms too now - it's useful for every discussion.
You explained how You uderstand REPROGRAMING. May be it is possibe interpretation of this BASIC term more wide. First - AUTONOMOUS REPROGRAMMING. This means - HUMAN taking some mixture starts some process inside the body. Becouse of lost informtion only partial result of AUTINOMUOS REPROGRAMMING is expected as YOU defined. The other possibility - Human takes the start REPROGRAMMING mixture, but using the genes target therapy too he tries to RENOVATE the lost pattern of methylation status too - You mentioned the problem (for example that existed and was red and stored at the age of twenty) renovating the stem - immortal cells, that reproduces all the total body and all the lost cells during aproximately the year becouse the last suffered natural appotoses. This I call (kind of possible) CONTROLED REPROGRAMMING. Do You agree to use such partial meanings of basic term - REPROGRAMING:
- the AUTONOMOUS REPROGRAMMING
- or the other possibility - CONTROLED REPROGRAMMING?
The PROGRAM for me means the sequence of instructions which fullfilled leads to the necessary a priori defined state (computer science). What is the program in the biology? Something like fate dependent on basic gametas features. So these features define the development scenary which is extremly complex and huge to describe becouse of huge information about even the basic - the changes of the stem cells. We need to define and understand these basic terms when generating ideas and make agreement as deep as possible if we want to move forvard! Thank You for this real BRAIN STORM You initiated.

Edited by urba, 09 May 2010 - 04:01 AM.


#66 Hedrock

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Posted 09 May 2010 - 05:52 AM

The circle of problems we touched rises immediately becouse the system we investigate is unrealy wide and complex. this is only one - biochemical, not the biological and social level - ref.


Believe me! I studied the human body for decades. I know most of the processes in the linked picture.

Epigenetics is still little understood and often misinterpreted.

So for better understanding we must be not in a great hurry.


What???

I am in a hurry! Time is running me away.

If even the people in this platform do not recognise reasons of aging, which is undoubtedly epigenetics, you will not have much time, even if you are 18 years young.

Do You agree to use such partial meanings of basic term - REPROGRAMING:
- the AUTONOMOUS REPROGRAMMING
- or the other possibility - CONTROLED REPROGRAMMING?
The PROGRAM for me means the sequence of instructions which fullfilled leads to the necessary a priori defined state (computer science). What is the program in the biology? Something like fate dependent on basic gametas features. So these features define the development scenary which is extremly complex and huge to describe becouse of huge information about even the basic - the changes of the stem cells. We need to define and understand these basic terms when generating ideas and make agreement as deep as possible if we want to move forvard! Thank You for this real BRAIN STORM You initiated.


If you want to decide between autonomous and controlled reprogramming I assume you.

So I mean "autonomous reprogramming" in your phrasing. The term "DNA methylation reprogramming" was not created by me, but is a common term in biology for only one unique autonomous processes. You just can push the start-button (the two proteins Oct4 and Sox2). Everything else is running automatically.

I expanded the term "DNA methylation reprogramming" in so far as I think we can do partial reprogramming. Not full demethylation, just a bit. Remethylation by selected hormone.

So let me introduce 2 new terms:
- Full DNA methylation reprogramming (=cancer in an adult person)
- Partial DNA methylation reprogramming (=rejuvenation?)

Partial DNA methylation reprogramming could be controlled by the hormone you take/ you are navigating to. Every hormone starts a special reprogramming sequence. Insect hormones would start another gene sequence than DHEA. And the reprogramming sequence of estrogen which is the master starter sequence of human life would be too dangerous. The master process "estrogen" is identical to the cancer process - unfortunately. So we do not restart the master sequence but just some minor sequence which would rejuvenate us. From my view I would recommend the DHEA methylation reprogramming process in the beginning.

The program itself cannot be changed easily. Not in this century!

The first task is to survive!

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#67 Hedrock

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Posted 09 May 2010 - 06:44 AM

It is a fascinating topic indeed.

Is resveratrol a better HDAC-Inhibitor than sulforaphane?


I don't know. Maybe sulforaphane is underrated?

But it's much easier to take sulforaphane rich food than resveratrol rich food. So this could be a nutritional approach. Eat more cruciferous vegetables and soy. :|?

This study looked at soy, EGCG, and sulforaphane.


Interesting article. Haven't seen it yet, but it shows me I'm on the right way. Thank you!

#68 urba

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Posted 09 May 2010 - 06:59 AM

If you want to decide between autonomous and controlled reprogramming I assume you.

So I mean "autonomous reprogramming" in your phrasing. The term "DNA methylation reprogramming" was not created by me, but is a common term in biology for only one unique autonomous processes.

I expanded the term "DNA methylation reprogramming" in so far as I think we can do partial reprogramming. Not full demethylation, just a bit. Remethylation by selected hormone.

So let me introduce 2 new terms:
- Full DNA methylation reprogramming (=cancer in an adult person)
- Partial DNA methylation reprogramming (=rejuvenation?)


The first task is to survive!


Well, it becomes clearer. So, we are searching for REJUNEVATING DNA METHYLATION REPROGRAMMING and it is in our studies CANCEROUES DNA METHYLATION REPROGRAMMING. This sounds little better, I suppose. Please, describe REJUNEVATING DNA METHYLATION REPROGRAMMING (hypothesis ) possible starting tactics You propose in some classification style:
1.
1.1
1.2.
....
2.
....
for better understanding and more effective discussion becouse we must define strong and weak sides of method. We see THE STRATEGY You propose, but generals are nothing without the MAJORS solving tactical tasks! The other very attractive problem is, that those mixtures switches on important additional paralel processes. May be not only via DNA methylation changes.

#69 Hedrock

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Posted 09 May 2010 - 07:12 AM

@urba

Read this for clearing some basic questions. :|?

#70 urba

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Posted 09 May 2010 - 09:26 AM

Believe me! I studied the human body for decades. I know most of the processes in the linked picture.

Epigenetics is still little understood and often misinterpreted.

I am in a hurry! Time is running me away.

If you want to decide between autonomous and controlled reprogramming I assume you.

So let me introduce 2 new terms:
- Full DNA methylation reprogramming (=cancer in an adult person)
- Partial DNA methylation reprogramming (=rejuvenation?)

From my view I would recommend the DHEA methylation reprogramming process in the beginning.

The program itself cannot be changed easily. Not in this century!


Sir, YESTERDAY You anounced:
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.


TODAY - From my view I would recommend the DHEA methylation reprogramming process in the beginning.

So, for better understanding YOUR ideas it is possible make the SYSTEM of possible the renuvenating tactics initiations:

REJUNEVATING INITIATION STARTERS proposed by Hr CLASSIFICATION SYSTEM
1.The main - full
1.1. Epigenetic initialisation be Resveratrol + EGCG + Honokiol, the king supplements! EGCG could be replaced by parthenolide.

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

ADDITION: estrogens + DHEA (the both most important reprogramming starters),D3, melatonin, phytoestrogens and ecdysteroids.

....
2.Partial single
2.1- Demethylation - DHEA - reprogramming sequence

2.2- Demethylation - melatonin - reprogramming sequence
....
3. partial complex.
.......
(in cybernetical terms this means INPUT signal classification)

Is it right? Are there more partial subsets You propose could be efficient practically?
--------------------------------------------------------------------------------------
I'm mathematician (applied) and I like order, strict as clear as possible definitions, axiomas, theories, deduction, induction and strict usage of well defined terms and classifications for the more efficient discussion aim.
Biologists unfortunately uses not enough amount of models and bad defined unclear and fuzzy terms and this leads for lots of speculations. Sometimes I'm very sceptical about their style of thinking. You could see even different understanding of oncogene too. To avoid these difficulties better to make some systematization in the beginning, otherwise the doom of this discussion is LITTLE and SLOW MOVING FORWARD. Thanks anyway.

Edited by urba, 09 May 2010 - 09:27 AM.


#71 Hedrock

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Posted 09 May 2010 - 10:46 AM

Is it right? Are there more partial subsets You propose could be efficient practically?
--------------------------------------------------------------------------------------
I'm mathematician (applied) and I like order, strict as clear as possible definitions, axiomas, theories, deduction, induction and strict usage of well defined terms and classifications for the more efficient discussion aim.
Biologists unfortunately uses not enough amount of models and bad defined unclear and fuzzy terms and this leads for lots of speculations. Sometimes I'm very sceptical about their style of thinking. You could see even different understanding of oncogene too. To avoid these difficulties better to make some systematization in the beginning, otherwise the doom of this discussion is LITTLE and SLOW MOVING FORWARD. Thanks anyway.


Sorry, but why this pedantic push?

I'm also a mathematical person (software developer) but I have a more the 3-dimensional visual thinking. I imagine the molecules before me and often I understand how they react. So writing my imagination down in english (not my mother language) would be already an enormous efford.

It would be nice if you don't press me into your categorizing system.

I hate strict order --> it is killing everything creative

#72 urba

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Posted 09 May 2010 - 11:34 AM

Sorry, but why this pedantic push? I hate strict order --> it is killing everything creative

I hate too, but sometimes this helps to hit old order. Karl Jaspers told - if we don't want to loose our lifes we need some order... Possibilities of different partial intake mixtures could be interesting for poor people, for example and more mild reprograming.

#73 kafkastoaster

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Posted 09 May 2010 - 12:54 PM

Hearkening back to the first page, I feel I should point out this piece- which at the bottom begins to sound somewhat like a superhero origin story.

Epigenetics famously set back the pet cloning industry quite a bit when as part of a 3.7 million dollar project Rainbow the kitten was replicated and the new version came out completely different in build, coat, and personality thanks to changes in methyl group expression. That is my favorite industrial bioscience story.

#74 urba

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Posted 09 May 2010 - 02:58 PM

From my view I would recommend the DHEA methylation reprogramming process in the beginning.


What about this -
Conversely, treatment with parathyroid hormone, a hormone known to activate the CYP27B1 gene8, induces active demethylation of the 5mCpG sites in this promoter.

#75 VidX

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Posted 09 May 2010 - 06:13 PM

Ok, not to promote the irresponsible use of any of these hormonal or not substances, Hedrock, as you take them anyway - have u noticed any subjective effects worth mentioning?
Relaly interesting topic, and being a bodybuilder myself I have a certain fetish for "substances". Being ready to take even "desperate" action is in the plan of my game, however it may sound. This seems to be one of the paths to prepare in advance (if it's possible) if the situation becomes not well in terms of personal experience of ageing.

Edited by VidX, 09 May 2010 - 06:17 PM.


#76 Hedrock

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Posted 09 May 2010 - 06:24 PM

Hypothesis 2: Hormones are the starters of the reprogramming sequences and we must not go all the way back. We can go back just to some defined milestones.


In the fetus estrogens dominate in the first weeks. Later the fetus itself produces high DHEA amounts. Then later estrogen (if female) or testostosterone (if male) lead to the primary sexual development (if it's a girl or a boy).

The effects of these hormones are different than in an adult person, cause cells are not high differenciated in fetus. The CpG islands are not high methylated so the hormones do have different effects than in adult (methylated) persons. The methylation protects adult from the too high developmental effects.

Articles about development and hormones: estrogenic imprinting, progesterone, IGF, cortisol, PGE2, DHEA, androstenedione, testosterone and many more. Remember there are many, many hormones.

Up to now this is normal scientific knowledge.

So now to the unproved hypothesis:

It is possible after partial CpG demethylation to start a reprogramming sequence by a special hormone. The effect of the hormone on the CpG undermethylated cell would be totally different than in a normal methylated cell, There could in a positive or a negative effect of the hormone.

Partial reprogramming would be possible by this way, if well done.

#77 Hedrock

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Posted 09 May 2010 - 06:51 PM

Ok, not to promote the irresponsible use of any of these hormonal or not substances, Hedrock, as you take them anyway - have u noticed any subjective effects worth mentioning?


The goal should be not to add the hormones itself from extern sources but to lead the body by life style, nutrition and supplements to the production of the right hormones. Too much hormones wouldn't be good so it's better to balance the body out.

E.g.: Inhibit the production of too much bad DHT (dihydrotestosterone) by some plant extracts or high zinc.

Also there are plant extracts to highen body-produced DHEA (yams, fenugreek.. ).

But it's not possible in any case. For melatonin I do not know any natural replacement. So the melatonin has high uses in older people.

#78 VidX

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Posted 09 May 2010 - 07:31 PM

Are you aware about any attempts to try this or a similar thing on animals yet?

#79 Hedrock

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Posted 09 May 2010 - 07:45 PM

Are you aware about any attempts to try this or a similar thing on animals yet?


No! How can anybody have tried it, if I am the person who has found it out first, that partial reprogramming is possible?

#80 VidX

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Posted 09 May 2010 - 07:52 PM

Are you aware about any attempts to try this or a similar thing on animals yet?


No! How can anybody have tried it, if I am the person who has found it out first, that partial reprogramming is possible?



Oh ok, I still need to do much reading to get the idea how much is known about this.

So it seems like it would be a pretty interesting experiment, even if it's kinf of a "shot in the dark" testing of a hypothesis, while searching for the right compunds to get the wanted/presumed effect.
Anyone have a hamster or something? :|?

j/k

Edited by VidX, 09 May 2010 - 07:53 PM.


#81 Hedrock

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Posted 09 May 2010 - 08:09 PM

So it seems like it would be a pretty interesting experiment, even if it's kinf of a "shot in the dark" testing of a hypothesis, while searching for the right compunds to get the wanted/presumed effect.
Anyone have a hamster or something? :|?

j/k



I already started injecting myself procaine (a DNMT1-inhibitor) daily. But I stopped it out, because I couldn't find anyone doing something like this. Long-time users of procaineamide (a different substance) developed Lupus erythematus. This effect is not known from procaine and it seems to be pretty safe, but I suddenly felt some uncertainty.

So I thought some theoretical work could be useful before the start.

Procaine is a wunderful substance because the local application is so easy. You could inject it into your left hand and if the left hand rejuvenates compared with the right hand it is working. :)

Edited by Hedrock, 09 May 2010 - 08:13 PM.


#82 Elus

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Posted 10 May 2010 - 01:32 AM

I sent Aubrey an e-mail, asking him whether or not TA-65 would be an effective way to combat aging. He forwarded my e-mail to a colleague who replied with the following:



Hi Nikolay,
>
> Do you have any thoughts about the 'telomere lengthening' supplement
> sold by this company? http://www.tasciences.com/
> Supposedly the supplement, TA-65, activates telomerase in somatic
> cells. Would this be a practical way to combat aging?

I'm afraid not, for several reasons. In addition to the fact that it's
quite unproven to do what it claims to do even in the very narrow sense
(activating telomerase in people swallowing the capsults), it also
wouldn't do much to affect aging even if it did, and could actually be
dangerous for a specific, very important age-related disease: cancer.

First, we don't yet know that TAT2/TA-65 can lengthen telomeres in
vivo. I don't actually believe that this has actually been reported:
their only published report ( J Immunol. 2008 Nov 15;181(10):7400-6) is
of an in vitro experiment with human CD8+s taken *from* an HIV+ patient,
not in vivo or even ex vivo after oral administration of the compound.

They've shown that when they've mixed the stuff, in a *test tube* , with
white blood cells from HIV patients (whose white blood cells have
abnormally shortened telomeres, because the virus forces them to
replicate those cells which wears the telomeres down), TAT2/TA-65
activates telomerase in those white cells and brings their
pathogen-killing function (again, in a test tube) closer to cells from
normal healthy people.

But this doesn't prove that the same thing would happen to these HIV
patients (let alone normal, healthy people) after swallowing a *pill*
with TA-65: phytochemicals are, notoriously, extensively modified in the
gut and liver by the same enzymes that detoxify various toxins and
drugs, which often either blocks their absorption or drastically changes
their bioactivity once they actually reach the cells of the body through
the circulation. And, moreover, the fact that (broken record! -- *in a
test tube* ) these HIV patient cells have a *more normal* cell-killing
ability; that doesn't show that a person with *normal, healthy* white
cells would get an *even greater* cell-killing capacity (even in a test
tube :|? ) under the same conditions.

This, obviously, in itself dampens enthusiasm, as (from the perspective
of the biogerontology community) does the fact that the patient is HIV+,
and thus has CD8+ cells that are already defective because of the
stressful systemic environment, so that -- even if the effects in vitro
were to translate into a result in vivo -- the *relative* increase in
telomere length, cytokine production, and virus-killing activity may be
of no significance to people with normal T-cell function, or with
age-related impairments unrelated to those in this HIV+ patient.

This leads into the second and broader question of whether activating
telomerase would actually provide any benefits to "normally" aging
people. Since the early excitement raised by the initial discovery of
telomerase in the context of the early, simplistic model of replicative
senescence on which it was superimposed (the "Hayflick limit"), our
understanding of both cellular senescence and its relationship to
organismal senescence has expanded quite a bit. While the popular press
continues to promote the idea that we age because our cells run out the
proliferative capacity by running up against critically-shortened
telomeres, there's very little support in the scientific community today
for either the proposition that cellular senescence is predominantly the
result of telomere erosion, or that replicative arrest per se makes a
major contribution to organismal aging. See:


Hopkin K.
More than a sum of our cells.
Sci Aging Knowledge Environ. 2001 Oct 3;2001(1) : oa4. Review.
PMID: 14602948 [PubMed - indexed for MEDLINE]

Hornsby PJ.
Mouse and human cells versus oxygen.
Sci Aging Knowledge Environ. 2003 Jul 30;2003(30):PE21.
PMID: 12890857 [PubMed - indexed for MEDLINE]

(The above two are intend for the educated layperson; here's one that's
more challenging:

Patil CK, Mian IS, Campisi J.
The thorny path linking cellular senescence to organismal aging.
Mech Ageing Dev. 2005 Oct;126(10):1040-5.
PMID: 16153470 [PubMed - indexed for MEDLINE]

Finally, and most importantly, even if it works systemically after oral
administration, and even if it did provide benefits to at least some
aspects of aging, systemic delivery of a compound that (putatively)
activates telomerase makes a lot of people (myself and Dr. de Grey
included) very nervous, for the simple reason that telomerase activation
could open up the proliferative barrier for preneoplastic cells to push
over the limit imposed by 'crisis' and programmed senescence and acquire
the additional mutation(s) required to become fully-fledged malignant
cancer cells. Part of the reason we have telomeres wearing down in our
cells in the first place is to prevent runaway cell proliferation -- in
other words, cancer. In fact, cancer cells can't survive without
acquiring mutations that allow them to keep lengthening their telomeres
as they divide furiously, and they most often do this exactly by
activating telomerase! These companies point to studies that show that
activating telomerase doesn't *cause* the cells to become cancerous, but
that's not the point: doing so gives *precancerous* cells the
*opportunity* to keep replicating themselves, acquiring new mutations
and eventually becoming full-blown cancers, by taking off the cell's
ultimate braking system for cell division. Bypassing this strict control
by a drug or supplement is really asking for trouble.

More on this here:

http://www.mfoundati...hread.php?t=437

http://www.mfoundati...e...1243&page=2

http://www.mfoundati...e...1243&page=2

> P.S. Happy new year.

And to you -- and many, many more! And , if you're ready to help us to
increase your odds of enjoying those additional years by hastening
progress in SENS science, we have quite a few listed here:

http://sens.org/inde...donations_other

Also, you can pick up a copy of Aubrey's and my book (link above) and,
after having read it for your own further understanding, get the word
out by passing your copy around to others you know, and/or by donating
it to a library, and/or by picking up extra copies for the latter 2
purposes.

And (naked plug!) remember that you can help to ensure that real
age-reversing biotechnology becomes available as soon as possible,
alleviating the most age-related suffering and death, by making a
donation to support SENS research:

http://sens.org/inde...onations_donate

I leave it to you to choose how you will take on the moral and
scientific challenge of biological aging. However you proceed: live long
-- live young!

-Michael
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#83 urba

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Posted 10 May 2010 - 05:41 AM

>
> Do you have any thoughts about the 'telomere lengthening' supplement
> sold by this company? http://www.tasciences.com/
> Supposedly the supplement, TA-65, activates telomerase in somatic
> cells. Would this be a practical way to combat aging?


First, we don't yet know that TAT2/TA-65 can lengthen telomeres in
vivo.
-Michael


In ageing problem only the stem cells must be considered becouse they reborn all the rest cell aproximately during the year

#84 Hedrock

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Posted 10 May 2010 - 06:01 AM

In ageing problem only the stem cells must be considered becouse they reborn all the rest cell aproximately during the year


Any evidence for this?

In my new stream, the "DNA Reprogramming Section of Immortalists" :|? the goal is to reprogram all tissues. This means not only the stem cells but all kinds of cells. The idea that only renewing the stem cell would be enough, was rejected by me in the last time. Stem cells are important and indispensable but they could not repair all the other junk. If the majority is (epigenetic) old tissue - junk - you will die, even if all of your stem cells are intact.

#85 urba

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Posted 10 May 2010 - 06:01 AM

The term "DNA methylation reprogramming" was not created by me, but is a common term in biology for only one unique autonomous processes. You just can push the start-button (the two proteins Oct4 and Sox2). Everything else is running automatically.

The term "DNA methylation reprogramming" is not very succesfull one. Where and what is the program in this case? The more precise term could be taken from Probabilstic Automata theory - this is system state revers, so "DNA methylatiion state reverse" could be used too for better understanding, but biologists who haven't heard anything about automata and control theory but heard something about programming let into the world the term 'reprogramming" and this "infection' of 'reprogrammng uisage' wide spreaded. I've found interesting article about "reprogramming into i-polipotent cellref using Oct4 Sox2 and some demethylating drug too.
this one "Immortality improves cell reprogramming" ref is very interesting too. Thanks.

#86 urba

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Posted 10 May 2010 - 06:09 AM

In ageing problem only the stem cells must be considered becouse they reborn all the rest cell aproximately during the year


Any evidence for this?

In my new stream, the "DNA Reprogramming Section of Immortalists" :|? the goal is to reprogram all tissues. This means not only the stem cells but all kinds of cells. The idea that only renewing the stem cell would be enough, was rejected by me in the last time. Stem cells are important and indispensable but they could not repair all the other junk. If the majority is (epigenetic) old tissue - junk - you will die, even if all of your stem cells are intact.


I mean Adult man stem cells which exist in all the tissues and reborn all the tissues during the year when old cells (1012 permanently are dying becouse of appoptosis. If we reunevate well differentiated cells they will live the most time aproximately only the year, so they are not real target for the long term reYOUNGERstateRETURN but the origin - Quelle - stem is.

#87 Hedrock

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Posted 10 May 2010 - 06:24 AM

I mean Adult man stem cells which exist in all the tissues and reborn all the tissues during the year when old cells (1012 permanently are dying becouse of appoptosis. If we reunevate well differentiated cells they will live the most time aproximately only the year, so they are not real target for the long term reYOUNGERstateRETURN but the origin - Quelle - stem is.


I don't think they are dying as fast as you think!

Again, give me sources that cells are replaced on a yearly base.

If they are dying and rejuvenating in a fast cycle as you think, you are right. Then only stem cells would limit aging.

But that's not the case. Body replaces cells slowly and often only does some repair. That is from an evolutionary point of state "efficient". Rejuvenating all tissues would cost lots of energy. Energy is rare in nature so the selection is more for reproduction than for rejuvenation.

Edited by Hedrock, 10 May 2010 - 06:25 AM.


#88 N.T.M.

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Posted 10 May 2010 - 06:33 AM

I sent Aubrey an e-mail, asking him whether or not TA-65 would be an effective way to combat aging. He forwarded my e-mail to a colleague who replied with the following:



Hi Nikolay,
>
> Do you have any thoughts about the 'telomere lengthening' supplement
> sold by this company? http://www.tasciences.com/
> Supposedly the supplement, TA-65, activates telomerase in somatic
> cells. Would this be a practical way to combat aging?

I'm afraid not, for several reasons. In addition to the fact that it's
quite unproven to do what it claims to do even in the very narrow sense
(activating telomerase in people swallowing the capsults), it also
wouldn't do much to affect aging even if it did, and could actually be
dangerous for a specific, very important age-related disease: cancer.


Eh, this is very disappointing.

Oh, and TA-65 should be administered intravenously, not orally.

As for cancer: I guess that precancerous tissue would then be permitted to proliferate further thus increasing its odds of becoming completely malignant. However if it hasn't acquired the necessary mutation to sustain telomerase activation apart from what the therapy provides, then once a tumor is detected the therapy could be temporarily discontinued while the tumor is excised. Afterwards, of course, it could be resumed while exercising the same vigilance.

Edited by N.T.M., 10 May 2010 - 06:35 AM.


#89 urba

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Posted 10 May 2010 - 07:14 AM

I mean Adult man stem cells which exist in all the tissues and reborn all the tissues during the year when old cells (1012 permanently are dying becouse of appoptosis. If we reunevate well differentiated cells they will live the most time aproximately only the year, so they are not real target for the long term reYOUNGERstateRETURN but the origin - Quelle - stem is.


I don't think they are dying as fast as you think!

Again, give me sources that cells are replaced on a yearly base.



This is the problem - "Some sources told us that the average adult human body is made up of "50 million million" (50 trillion) cells, while others put the figure closer to 10 trillion. Science NetLinks, a resource for science teachers, stated that there are approximately "ten to the 14th power" (that's 100 trillion) cells in the human body.

Keep in mind, all of these figures are just estimates"


wiki - from Apoptosis: 'Between 50 and 70 billion cells die each day due to apoptosis in the average human adult. For an average child between the ages of 8 and 14, approximately 20 billion to 30 billion cells die a day. In a year, this amounts to the proliferation and subsequent destruction of a mass of cells equal to an individual's body weight." Adult human consists of the 1012 cells, so the duration 1-10 year looks to be possibly true and human is real renovating factory. The stem cells really suffer long lasting aging, not the nromal differentiated cell. I'm just studying this problem.

Click HERE to rent this BIOSCIENCE adspot to support LongeCity (this will replace the google ad above).

#90 urba

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Posted 10 May 2010 - 07:44 AM

I mean Adult man stem cells which exist in all the tissues and reborn all the tissues during the year when old cells (1012 permanently are dying becouse of appoptosis. If we reunevate well differentiated cells they will live the most time aproximately only the year, so they are not real target for the long term reYOUNGERstateRETURN but the origin - Quelle - stem is.


I don't think they are dying as fast as you think!

Again, give me sources that cells are replaced on a yearly base.


The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (approximately 10% per year) or mean age of adipocytes (approximately 10 years) was not correlated with morphology.ref




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