115 replies to this topic

[Hedrock]

Just another aging theorie? Or the ultimate solution?

DNA Methylation Reprogramming (DMR)

Loss in methylation patterns occurs by aging. Methylation changes with time.

On the one side there are very important genes (p16 tumor suppressor gene) which are hypermethylated with time. This increases cancer risk.

On the other side many DNA regions are undermethylated. This lead to activation of bad genes. This could lead to metabolic diseases anc cancer too.

Possible ways to rejuvenation:


1.) Demethylation / Remethylation

The zygote does sometimes. And the cells survive and become healthy individuals.

Of course for an adult person this would be a very radical path including massive dangers of cancer / lupus erythematosus.

PMID 17676637

Danger are high. Maybe this path works only in zygotes?

2.) Generating induced pluripotent stem cell (iPS) by the oct4 sox2 klf4 c-myc pathway

oct4 sox2 klf4 and c-myc are proteins.

Normal cells of adult mice or human could be transformed to ploripotent stem cells.

Takahashi et al. were the first scientists who have proven the possibiliy: PMID 16904174


The second path seems to be more promising.

I would like to integrate more the idea of DNA reprogramming into the ImmInst-Forum. Interested?

[Hedrock]

Sorry, but without understanding the methylation process in aging, nobody will understand aging at all.

The difference between a young cell and an old cell is mainly in methylation, what is synonymous to the epigenetic process!

Of course telomerase would play a role too, if you are between 120 and 150 years old. Yes, there is a telomere frontier too. But aging between 0 and 120 years is controlled by epigenetics. I would say 90 % epigenetics and 10 % other reasons!!

I want to discuss here the basics in aging and the possible ways to reconstruct adequate young methylation patterns.

Key words: Undermethylation, overmethylation, reprogramming starter genes (master control genes), hormones, DHEA, melatonin, steroid hormones, epigenetic di- / tripeptide hormones, cholesterol, DMR = DNA methylation reprogramming.

Edited by Hedrock, 12 April 2010 - 07:29 PM.

[AgeVivo]

I am interested. Very interested. I think it can be key. If you want to present what you know on the subject in a Sunday Evening Update I will attend it.

[1kgcoffee]

I am very interested, but this is waaay beyond my expertise, sadly. Could you come up with a simple regimen for #2? I have heard that blue green algae stimulates the release of stem cells.

[Hedrock]

I am very interested, but this is waaay beyond my expertise, sadly.

Yes, I would like to deal all my knowledge with you.

But the problem ist: I don't like to be the clown in a one-man-show. What I'm searching is input and reflection about my ideas with other immortalists. Epigenetics is very difficult to understand, even for professionals in this field, so without detailed consideration one could easily go wrong. This is the most complex software in the world!

If only I would publish my ideas here, they could be terribly wrong, leading other people to some mistakes.

There must be someone to talk about. Doesn't need to be a gene technician or a biologist.

Could you come up with a simple regimen for #2? I have heard that blue green algae stimulates the release of stem cells.

It is probably not that apparently easy way just to swallow some pills! I assume we would need to extract some cells from your body and process them in some defined way. Then do some implantations.

Or if it's easier, we would need to inject a few substances, into your body. Maybe Infusions.

Are you ready for this?

Most "immortalists", whatsoever the meaning of this word is, are not ready for these massive intervention. I think most would not risk their live for immortality even if they would have a 50:50 chance.

Better take your guinea pig first before trying it yourself.

Yeah, it's ok!

I also will test with some animals, if the substances are new. Really! I am a bit crazy but not crazy at all. Some fear could save my life for experimenting 10 more years.

So just one word again to the "magic wonder pill":

Yes, many supplements are useful. I highly appreciate them.


But the problem ist: Many high effective substances are processed on the intestinal path. Proteins for example! How do you want to get proteins into your cells? So say goodbye to the idea of the immortal pill. Proteins have to be injected!

Of course we will need lot's of pills and supplements in addition, also an adequate nutrition, but this alone would not be enough to my opinion.

[Hedrock]

Wow, they have proven that in some cells Oct4 would be enough to generate pluripotent stem cells.

Direct reprogramming of human neural stem cells by OCT4

What a success!

Or even better:

We don't need stem cells. Just fibroblasts!

Induction of pluripotent stem cells from primary human fibroblasts with only Oct4 and Sox2


Even the cancer problem seem to be solved:

c-myc is the bad boy!

Stem Cells—This Time without the Cancer

iPS Without A Cancer-causing Virus Gene


So the new plan is:

Bring oct4 and sox2 into some cells. (Only some, please not all!)

Then you have enough young cells - not cancer!



Any idea if this could be enough?

What vector should we take?

Is there a path without vector?

Edited by Hedrock, 13 April 2010 - 09:49 PM.

[rwac]

How do you want to get proteins into your cells? So say goodbye to the idea of the immortal pill. Proteins have to be injected!

Liposomal delivery of substances is another possibility.

[Alpharius]

I am also very interested in this issue. There are several reasons for this, mostly because I don`t think, that "classic" mutations directly in our DNA is the cause for aging we are experiencing right now ( perhaps apart from mitochondrial DNA). DNA mutations would probably be a much bigger problem if we would live several hundred years, but in our lifetime I would say that epigenetic changes and disregulation of gene expression are more important.

What made this issue more interesting for me, is the existence of not aging (or extremly slow aging) animals. One good example is the rogheye rockfish, some examples of this species were found in an age between 200-300, remarkably with no signs of age or senescence, this could mean that apart from predators or other dangers they could potentially live much more longer. One reason for this could be a much better antioxidant defense and on this way prevention of mutagenesis, but we have seen, that genetic alterations of the antioxidant selfdefense (hSOD targeted to mouse mitochondria) or strong mitochondria targeted antioxidants (methylene blue or some substances made and tested by Skulachev) were able to prolong the lifespan, but only slightly. So I think that not aging animals have some other systems beside strong antioxidants, which allow them to keep their cells away from epigenetic changes like already mentioned global demethylation and regional hypermethylation.

Regarding the IPS stuff and inserting of pluripotency inducing proteins into cells: I would be very careful with such thoughts. I have worked in a lab which works on IPS and altough I can not go into detail, I just can say that inducing stem cells is not so easy, even in vitro. Otherwise it is also worth mentioning, that IPS can form teratomas, I would not feel safe even by throwing c-myc out. So trying to do something like that in vivo in a human would be very difficult and risky.

I hope also that this won`t become an one man show, but right now I still have to read a lot about epigenetics (now reading: Chromatin and Gene Regulation, Epigenetics of Aging), I also have to read a lot for my studies, so I don`t know if I can already contribute a lot, but I will try.

[N.T.M.]

But aging between 0 and 120 years is controlled by epigenetics. I would say 90 % epigenetics and 10 % other reasons!!

I'd have to disagree. Important, yes. But still overstated imo.

I am also very interested in this issue. There are several reasons for this, mostly because I don`t think, that "classic" mutations directly in our DNA is the cause for aging we are experiencing right now ( perhaps apart from mitochondrial DNA). DNA mutations would probably be a much bigger problem if we would live several hundred years, but in our lifetime I would say that epigenetic changes and disregulation of gene expression are more important.

Agreed.

Edited by N.T.M., 14 April 2010 - 10:18 AM.

[Hedrock]

Liposomal delivery of substances is another possibility.

Good idea.

What animal would be the best to test the liposomal delivery? I think it should be one without hairs?

I have worked in a lab which works on IPS and altough I can not go into detail, I just can say that inducing stem cells is not so easy, even in vitro. Otherwise it is also worth mentioning, that IPS can form teratomas, I would not feel safe even by throwing c-myc out. So trying to do something like that in vivo in a human would be very difficult and risky.

Yes, it is risky! You are right.

But look at nature.

The nature has tried million of years to create an human immortal being. Result was only cancer till now. But nature just created two higher immortal animals. The one is a jellyfish species. the other is the sea cucumber (not sure, but very long-living anyway!). It needed many million years but it was successful in the end.

The mechanisms of both are different but both involving epigenetics.

- The jellyfish by cyclic epigenetic reprogramming
- The sea cucumber by two mechanisms: continously high saponin levels (toxic to human but not to the sea cucumber), continously reprogramming and loosing abundant tissue - throwing away their intestinal tract!

Transdifferentiation is the key word here!

We just need to copy nature - why has nobody done yet? I want to do!

Why am I swallowing tons of ginseng, jiaogulan and other plant saponins? Because I copy the sea cucumber. But saponins are only one important key to epigenetics! It does only the half job. There must be another important key. I think the epigenetic program ends in the nowhere! It has never been completed cause men died early so there was no selection for longvity.

What is aging else than epigenetics?

Let's discuss reprogramming. Just theoretical in the beginning - but this is the only way that will work!

But aging between 0 and 120 years is controlled by epigenetics. I would say 90 % epigenetics and 10 % other reasons!!

I'd have to disagree. Important, yes. But still overstated imo.

What else would be the aging mechanism?

- Oxidation? No!
- Intracellular junk? No!
- Glycation? Yes, in some tissues: eyes, skin... , but not in all, it is a part itial reason but not the main reason!
- Telomere shortening? No.. we die before this happens in most cells. But it will play a big role if we would be older.

So if you know, please explain me what aging is!

I can explain you aging in a simple picture:

Aging is

Start Program -- 1 -- 2 -- 3 -- 4 -- 5 -- 6 -- 7 -- 8 -- End Program

Long live is:

Start Program ---- 1 ---- 2 ---- 3 ---- 4 ---- 5 ---- 6 ---- 7 ---- 8 ---- End Program


But it never reverses except in the special quail or the sea cucumber!

So aging is nothing else than a one way program. Imperfect programming. The programmer started to write a program, but he never completed it!

A cycle would be perfect.

Do you understand me?


P.S. Lots of corrections. My english is not the best. Sorry!

Edited by Hedrock, 14 April 2010 - 10:24 PM.

[rwac]

What animal would be the best to test the liposomal delivery? I think it should be one without hairs?

Liposomes can be taken orally, you know. Liposomal vit C, Liposomal glutathione, etc.

[Hedrock]

What animal would be the best to test the liposomal delivery? I think it should be one without hairs?

Liposomes can be taken orally, you know. Liposomal vit C, Liposomal glutathione, etc.

You are right.

My english is very bad. So sometimes I misunderstand. Or is it the old brain? Sorry for that!

Edited by Hedrock, 14 April 2010 - 10:10 PM.

[acrossuniv1]

I am interested. Thank you for posting and raising this topic.

I have a little bit of science training in DNA methylation study. I would like to say some opinions here.

1. There has been many data/research indicating as people age, their DNA methylation pattern changes. What exactly are the changes, how to describe the change of patterns, need further research.

2. It is possible, and actually very probably, that DNA methylation is at least one of the causes of aging. We need more research to clearly demonstrate a/ a significant amount of genes importantly associated with aging is silenced due to methylation (or activated due to loss of methylation) when people getting old. b/ change of methylation status can change the pattern/speed of aging.

3. de-methylation to postpone/reverse aging could be tricky, because it seems what important in aging is not just "more methylation", but "abberrant methylation". The way to treat "abberrant methylation patterns" may need as much information as complex as correcting all the gene mutations in aging cells. But that is not to say de-methylation is not hopeful, we need more research and more try to see if it works.

4. interestingly, some herbal/natural ingredients may have effects on methylation. Ginseng is a herb which is said to have some life-prolonging effect in folk cultures. I have used ginsenoside (major effective chemical in ginseng) to treat cell culture and found it has a weak anti-methylation effect. Although the effect was very weak that the project was dropped instead focused on more official de-methylation drugs such as 5-Aza-deoxycytidine, it was interesting to me to observe the coincidence. Will gensing be useful in demethylation regimen?--it is really not sure at this moment and better not to draw any over-confident conclusions.

Overall speaking, more research is needed. I like this thread and topic and will be interested in participate more. In the meantime, I am looking for a real lab experiment position to do research on it, or write a grant to get funding. If anyone interested or have the resource, please kindly let me know.

Edited by acrossuniv1, 15 April 2010 - 12:02 AM.

[acrossuniv1]

Any idea if this could be enough?

What vector should we take?

Is there a path without vector?

No matter what idea is and how good the mechanism/experiment systems are, finally it need to be tested in real people (clinical trials). Sometimes it works in lab but not work in human, just like some other gene therapies. However, one should not deny it as possible way of anti-aging, and I believe what we need is many hard work, that's all.

Edited by acrossuniv1, 15 April 2010 - 12:16 AM.

[acrossuniv1]

Any idea if this could be enough?

What vector should we take?

Is there a path without vector?

No matter what idea is and how good the mechanism/experiment systems are, finally it need to be tested in real people (clinical trials). Sometimes it works in lab but not work in human, just like some other gene therapies. However, one should not deny it as possible way of anti-aging, and I believe what we need is many hard work, that's all.

[acrossuniv1]

But aging between 0 and 120 years is controlled by epigenetics. I would say 90 % epigenetics and 10 % other reasons!!

I'd have to disagree. Important, yes. But still overstated imo.

I agree, 90% controlled by epigenetics is probably overstated.

[1kgcoffee]

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?

[acrossuniv1]

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?

I do not take it and I do not have much knowledge about it. Try google "ginseng" and find more information about.

[N.T.M.]

What else would be the aging mechanism?

- Oxidation? No!
- Intracellular junk? No!
- Glycation? Yes, in some tissues: eyes, skin... , but not in all, it is a part itial reason but not the main reason!
- Telomere shortening? No.. we die before this happens in most cells. But it will play a big role if we would be older.

So if you know, please explain me what aging is!

We don't merit the effects of chromosome shortening within current life spans because we die before their length starts to become deleterious (fraying ends, etc.). As for glycation: I'd say it's a huge part and prevalent throughout our body. It reduces blood vessel plasticity, shackles down the body's natural repair mechanisms, degrades skin elasticity, etc. AGEs are major.

Oh, and intracellular aggregates. Contrary to what you're saying, in non-dividing cells (since there's no replication to dilute their accruement) intracellular aggregates' accumulation grows to eventually impede the cells' functions. Extracellular aggregates are important too because they'll eventually choke out cells.

These all interact synergistically to culminate in the exponential decline in health which we call aging. There are other aspects too of course, but those are the most prominent I believe.

As for methylation: I'm not sure whether it's an underlying cause or just a subsequent issue resulting from one. I'm inclined to believe the latter.

Edited by N.T.M., 15 April 2010 - 09:19 AM.

[Hedrock]

Hey N.T.M.,

thank you a lot for your answer.

We don't merit the effects of chromosome shortening within current life spans because we die before their length starts to become deleterious (fraying ends, etc.).

Ok, so far!

But I will not wait with telemere lengthening till I'm 120. Better to start earlier!

In an older age it would be sure a problem.

As for glycation: I'd say it's a huge part and prevalent throughout our body. It reduces blood vessel plasticity, shackles down the body's natural repair mechanisms, degrades skin elasticity, etc. AGEs are major.

I agree to some points of you. Glycation blocker help a lot in keeping health. The effect on the skin is wunderful! You will have a smooth skin and less wrinkles. And yes, good for the blood vessels. I appreciate Carnosine a lot for its obvious effects. But will it stop aging? Delay maybe! But reverse never!

It is a good think to stop glycation for the symtoms of aging and for general health.

Carnosine is one of the best supplements for health we have!

I take it both. From inside and outside (topical skin care with carnosine every day).

But glycation not the main reason.

Oh, and intracellular aggregates. Contrary to what you're saying, in non-dividing cells (since there's no replication to dilute their accruement) intracellular aggregates' accumulation grows to eventually impede the cells' functions. Extracellular aggregates are important too because they'll eventually choke out cells.

These all interact synergistically to culminate in the exponential decline in health which we call aging. There are other aspects too of course, but those are the most prominent I believe.

I'm much more afraid before junk cells.

If regenerated cells were dividing more often, there would be no intracellular junk. There would be some old junk inactive cells. And the "young" cells derived from stem cells. So how to get rid of all these old cells?

The sea cucumber has found a solution: It throws its gut away regularly followed by a full regeneration of the intestinal tract. Fascinating!

As for methylation: I'm not sure whether it's an underlying cause or just a subsequent issue resulting from one. I'm inclined to believe the latter.

My opinion is still: Epigenetics is the main reason.

Maybe I was too radical in the beginning. So let's make a compromise:

50% Epigenetics
30% Junk: Intracellular junk, extracellular junk + old inactive cells
20% glycation

Is it good now?

How can I prove you that epigenetics is an important reason for aging? Would a few articles be enough?

Imagine the genes have on/off buttons. These on/off buttons are pushed by accident on or off with no intelligence. What would be the result of this incidence?

[Hedrock]

Hi acrossuniv1,

and welcome here. I'm not a member here but I plan it to be, cause I spend a lot of time studying the regimens and the theories of the people here.

It is so exciting what happens in science at the moment.

I am interested. Thank you for posting and raising this topic.

I have a little bit of science training in DNA methylation study. I would like to say some opinions here.

1. There has been many data/research indicating as people age, their DNA methylation pattern changes. What exactly are the changes, how to describe the change of patterns, need further research.

Yes! Nobody knows it in detail. We are all just approximating to truth, but have not reached it yet.

I want to make a statement: Epigenetics and the genes itself are the most complex program-like process we know.

A programmer would be the right man to solve the mystery. I am a computer specialist (software development) and nutrition scientist. So I have some basic knowledge, but unfortunaly I'm not that specialist I would like to be,

2. It is possible, and actually very probably, that DNA methylation is at least one of the causes of aging. We need more research to clearly demonstrate a/ a significant amount of genes importantly associated with aging is silenced due to methylation (or activated due to loss of methylation) when people getting old. b/ change of methylation status can change the pattern/speed of aging.

Agree

3. de-methylation to postpone/reverse aging could be tricky, because it seems what important in aging is not just "more methylation", but "abberrant methylation". The way to treat "abberrant methylation patterns" may need as much information as complex as correcting all the gene mutations in aging cells. But that is not to say de-methylation is not hopeful, we need more research and more try to see if it works.

Full agree!

4. interestingly, some herbal/natural ingredients may have effects on methylation. Ginseng is a herb which is said to have some life-prolonging effect in folk cultures. I have used ginsenoside (major effective chemical in ginseng) to treat cell culture and found it has a weak anti-methylation effect. Although the effect was very weak that the project was dropped instead focused on more official de-methylation drugs such as 5-Aza-deoxycytidine, it was interesting to me to observe the coincidence. Will gensing be useful in demethylation regimen?--it is really not sure at this moment and better not to draw any over-confident conclusions.

Ginsenosides are very interesting in their structure. Like steroid hormones a bit.

I think they dock at cell nucleus and lead to the expression of something. It is more the selective way. Not just demethylation.

Of course ginseng will not make you an immortal. There must be something more than just ginseng! But maybe it does in men what the holothurin does in the sea cucumber! There are only two interesting animals who can create saponins: The sea cucumber and the starfish. Both have a very high regeneration potential!

Overall speaking, more research is needed. I like this thread and topic and will be interested in participate more. In the meantime, I am looking for a real lab experiment position to do research on it, or write a grant to get funding. If anyone interested or have the resource, please kindly let me know.

Agree! More research in this subject!

This will happen if more people recognise the importance. Curative medicine has seen the importance but I am missing it a bit in this platform.

Even Aubrey the Grey does not see epigenetics as a main reason:

7 types of aging

1. Cancer-causing nuclear mutations/epimutations

These are changes to the nuclear DNA (nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA. Certain mutations can lead to cancer, and, according to de Grey, non-cancerous mutations and epimutations do not contribute to aging within a normal lifespan, so cancer is the only endpoint of these types of damage that must be addressed.

With the normal mutations in DNA I agree with Aubrey, but with epimutations I disagree! Changes in epigenetics (programmed and by accident - both) make the big difference in my opinion!


I would like to study again my third course of studies at a future time. Genetics or gene technology. Oh my god, I must be crazy at all! Don't know if I can realize this!

[Hedrock]

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!

Edited by Hedrock, 15 April 2010 - 08:31 PM.

[VidX]

I was about to get more into epigenics recently as I have very little understanding of how it works so I can't contribute yet, but it's very interesting, definitely keep this discussion going.

[rwac]

Genistein, Daidzein, Glycitein

Watch out. Soy may have problems associated with it.

http://lpi.oregonsta...yiso/index.html

[Hedrock]

Please be aware that known supplements will not do the big changes in epigenetics.

Supplements are not the same as DNA reprogramming!

Reprogramming would do great changes in a short time! Supplements would only change some limited regions in your epigenetics and slowly.

[Hedrock]

Watch out. Soy may have problems associated with it.

Ok, thank you!

[N.T.M.]

Hey N.T.M.,

thank you a lot for your answer.

We don't merit the effects of chromosome shortening within current life spans because we die before their length starts to become deleterious (fraying ends, etc.).

Ok, so far!

But I will not wait with telemere lengthening till I'm 120. Better to start earlier!

In an older age it would be sure a problem.

As for glycation: I'd say it's a huge part and prevalent throughout our body. It reduces blood vessel plasticity, shackles down the body's natural repair mechanisms, degrades skin elasticity, etc. AGEs are major.

I agree to some points of you. Glycation blocker help a lot in keeping health. The effect on the skin is wunderful! You will have a smooth skin and less wrinkles. And yes, good for the blood vessels. I appreciate Carnosine a lot for its obvious effects. But will it stop aging? Delay maybe! But reverse never!

It is a good think to stop glycation for the symtoms of aging and for general health.

Carnosine is one of the best supplements for health we have!

I take it both. From inside and outside (topical skin care with carnosine every day).

But glycation not the main reason.

Oh, and intracellular aggregates. Contrary to what you're saying, in non-dividing cells (since there's no replication to dilute their accruement) intracellular aggregates' accumulation grows to eventually impede the cells' functions. Extracellular aggregates are important too because they'll eventually choke out cells.

These all interact synergistically to culminate in the exponential decline in health which we call aging. There are other aspects too of course, but those are the most prominent I believe.

I'm much more afraid before junk cells.

If regenerated cells were dividing more often, there would be no intracellular junk. There would be some old junk inactive cells. And the "young" cells derived from stem cells. So how to get rid of all these old cells?

The sea cucumber has found a solution: It throws its gut away regularly followed by a full regeneration of the intestinal tract. Fascinating!

As for methylation: I'm not sure whether it's an underlying cause or just a subsequent issue resulting from one. I'm inclined to believe the latter.

My opinion is still: Epigenetics is the main reason.

Maybe I was too radical in the beginning. So let's make a compromise:

50% Epigenetics
30% Junk: Intracellular junk, extracellular junk + old inactive cells
20% glycation

Is it good now?

How can I prove you that epigenetics is an important reason for aging? Would a few articles be enough?

Imagine the genes have on/off buttons. These on/off buttons are pushed by accident on or off with no intelligence. What would be the result of this incidence?

I actually drink 2-5 cups of green tea/day for its telemere-preserving effects. I don't believe it's been thoroughly corroborated, but it seems plausible. Maybe it's an effect of EGCG. That stuff's great.

Anyway regarding what you were saying about those supplements only mitigating the process (appose to reversing it): you're right. However, AGEs within the body can be broken, thus freeing up whatever tissues it fastened down. This has already been accomplished for one type of AGE by the use of the drug Alagebrium. Its effects were notable, however, glucosepane is far more ubiquitous. We need to create an AGE breaker for that particular adduct.

And I do concede that epigenetics are an important factor, but again, I believe that it’s likely that they’re just subsequent issues arising from underlying problems resulting from collateral damage imposed by metabolism. If you reverse the damage you presumably also rectify whatever problems it spawned (I’m guessing).

As far as culling senescent cells: if we could determine a “marker” that those particular cells carry it’d make it feasible to apply prodrugs. IIRC Aubrey proposed this for the issue of anergic T cells. And then of course we’d compensate for the cellular attrition by the introduction of stem cells.

Also, the enzyme telomerase renews telomere length, but if it’s not carefully modulated it can obviously result in cancer. Nanotechnology could conceivably do this eventually.

Edited by N.T.M., 16 April 2010 - 09:17 AM.

[Hedrock]

Anyway regarding what you were saying about those supplements only mitigating the process (appose to reversing it): you're right. However, AGEs within the body can be broken, thus freeing up whatever tissues it fastened down. This has already been accomplished for one type of AGE by the use of the drug Alagebrium. Its effects were notable, however, glucosepane is far more ubiquitous. We need to create an AGE breaker for that particular adduct.

Well, impressed of the visible action of Carnosin I thought like you time ago.

Of course breaking the glucosepane would give you a smoother skin and better blood vessels. But away from some optical sensations an old cell would stay an old cell! Old cells have some buttons in the state "off", whereas the button in young organisms is "on".

We should push the buttons - and be young again!

And I do concede that epigenetics are an important factor, but again, I believe that it’s likely that they’re just subsequent issues arising from underlying problems resulting from collateral damage imposed by metabolism. If you reverse the damage you presumably also rectify whatever problems it spawned (I’m guessing).

If your methylation pattern is lost- it IS lost anyway. Nothing will bring it back. Reprogramming would be a new start from a defined point. But the resulting pattern would be different!

There are only 3 possible ways:

1.) Prevention of methylation loss: In a theory B12, folate, SAMe shell prevent DNA from loosing the methylation pattern. Not sure if the theory is true. Maybe these nutrient could prevent some damage, but I have not seen evidence for this yet. But my mind is open: Give me scientific evidence that nutrients would prevent change in epigenetics. Copy errors of methylation could even happen with full loaded SAMe. Epigenetic changes could be part of the biological program.

2.) Reprograming:
a.) Mild variants: including steroid hormones, phytosteroids and saponins/triterpenoids. Would work inefficient and slowly, but are not very risky. One could have a try and many do.
b.) Hardcore variants: This is the real reprogramming (Methods like Oct4 + Sox2 I have mentioned before)


We could not neglect any point, but rejuvenation lies only in point 2 b.)!!!

Everything else would not stop aging.

There is nothing wrong with supplements, but the the big change comes from anywhere else!

Edited by Hedrock, 17 April 2010 - 08:58 AM.

[N.T.M.]

Anyway regarding what you were saying about those supplements only mitigating the process (appose to reversing it): you're right. However, AGEs within the body can be broken, thus freeing up whatever tissues it fastened down. This has already been accomplished for one type of AGE by the use of the drug Alagebrium. Its effects were notable, however, glucosepane is far more ubiquitous. We need to create an AGE breaker for that particular adduct.

Well, impressed of the visible action of Carnosin I thought like you time ago.

Of course breaking the glucosepane would give you a smoother skin and better blood vessels. But away from some optical sensations an old cell would stay an old cell! Old cells have some buttons in the state "off", whereas the button in young organisms is "on".

It's actually more than just an ostensible improvement. You see your body wants to repair itself, but AGEs impede those repair mechanisms. Breaking AGEs would then be reversing a major facet of aging. And since your body does not naturally cleave AGEs, ideal methylation patterns wouldn't help this particular problem.

There is nothing wrong with supplements, but the the big change comes from anywhere else!

Supplements buy time.

[Hedrock]

Sunday evening update:

DNMT1 inhibition and HDAC inhibition

Reprogramming only by chemical substances ?

Sox2 is dispensable for the reprogramming of melanocytes and melanoma cells into induced pluripotent stem cells

Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes

Needed:
1.) A DNMT1 inhibitor (e.g. Procaine, EGCG)
2.) A HDAC inhibitor (e.g. Valproic acid)

Small molecules boost reprogramming rates

Valproic Acid Stimulates Proliferation and Self-renewal of Hematopoietic Stem Cells

Valproic acid improves reprogramming efficiency by more than 100-fold


But a problem seems to be: SLE (Systemic lupus erythematosus) can be induced by valproic acid.

OMG: For valproic acid the same problem as with procaine. Not so funny.

The risk for metabolic diseases would be high by abuse of valproic acid.

Here for the interested: Some more chemical substances for Epigenetic therapy

Any comments?

Any ideas how to fix the metabolic and the autoimmunity problem?

Edited by Hedrock, 18 April 2010 - 07:10 PM.