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Stem cell self-renewal with C60

c60 stem cells mitochondria fusion stearic acid aging hydroxytyrosol olive oil mct oil proliferation

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#1771 Turnbuckle

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Posted 07 May 2022 - 03:19 PM

Supplementing with 100mg sulforaphane at T+30 would fix that, as sulforaphane does cross the BBB.

 

 

See this note from the last update:

 

7. I've dispensed with sulforaphane, but it might be helpful for some people. 

https://www.longecit...ndpost&p=914801

 

On the other hand, there's this: Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells

 

And this: Effects of sulforaphane on neural stem cell proliferation and differentiation

 
SFN of low concentrations stimulated cell proliferation and prominently increased neurosphere formation and NSC differentiation to neurons. SFN treatment upregulated Wnt signaling in the NSCs, whereas DKK-1 attenuated the effects of SFN. SFN is a drug to promote NSC proliferation and neuronal differentiation when used at low concentrations. These protective effects are mediated by Wnt signaling pathway.

 

 

Unfortunately there is a sweet spot, and using too much gets you nothing. 0.5 micromolar seems about right, but that is in vitro for 5 days. That is far beyond the half-life in vivo.


Edited by Turnbuckle, 07 May 2022 - 04:04 PM.

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#1772 Nate-2004

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Posted 07 May 2022 - 07:59 PM

Supplementing with 100mg sulforaphane at T+30 would fix that, as sulforaphane does cross the BBB.

 

Not sure if this is true, but I would like to see comparisons on stearic acid vs sulforaphane for fusion, definitely demands study.



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#1773 Turnbuckle

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Posted 07 May 2022 - 10:07 PM

Not sure if this is true, but I would like to see comparisons on stearic acid vs sulforaphane for fusion, definitely demands study.

 

 

Sulforaphane creates hyperfusion--

 

We demonstrate here that the mitochondria of cultured, human retinal pigment epithelial (RPE-1) cells treated with SFN undergo hyperfusion that is independent of both Nrf2 and its cytoplasmic inhibitor KEAP1. 

https://www.ncbi.nlm...les/PMC5126150/

 

 

Sulforaphane crosses the BBB

 

The results showed that sulforaphane and berberine have good oral bioavailability and would be predicted to cross through blood-brain barrier (BBB) easily, whereas the flavonoids in general would be predicted to be less effective in BBB transition because of their relatively high polar surface area.

https://pubmed.ncbi....h.gov/31322315/

 

 

Stearic acid does not cross the BBB--

 

Several areas of research have contributed to the establishment of a paradigm that meets the requirements for the selective uptake of essential polyunsaturated fatty acids (EPUFA) into brain. First, discrete studies have demonstrated that cholesterol and the nonessential fatty acids, (palmitic, oleic, stearic) do not enter the brain parenchyma. 

https://pubmed.ncbi....h.gov/31322315/

 


Edited by Turnbuckle, 07 May 2022 - 10:08 PM.

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#1774 anon2099

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Posted 12 May 2022 - 10:07 AM

https://pulmonaryfib...treatments-ipf/

 

Stem cells hold potential in treating diseases like IPF, where tissue is damaged and in need of repair. Airway basal stem cells, in particular, have shown an ability to grow new lung tissue after injury and to ease lung scarring in mice.

“However, cell survival is affected by the microenvironment during transplantation, and the efficacy of cell transplantation is a standing challenge,” the researchers wrote. Basal airway stem cells, specifically, “under oxidative stress in the alveolar microenvironment are poor in survival.”

CoQ10 was seen to protect cells against the stress induced by hydrogen peroxide and to result in fewer dead cells.

 

COQ10 may be Glutathione alternative. Shame, both are hardly absorbed by body unless formulated with a liposomal vehicle.

 


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#1775 nadaepeu

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Posted 17 May 2022 - 03:37 PM

Hello,

 

does anyone know a provider of dihydromyricetin in EU?



#1776 JPY

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Posted 17 May 2022 - 04:41 PM

Cerebra Nootropics: https://cerebra-noot...omyricetin-dhm/
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#1777 PAMPAGUY

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Posted 17 May 2022 - 04:52 PM

Hello,

 

does anyone know a provider of dihydromyricetin in EU?

https://www.google.c...6&bih=695&dpr=1



#1778 Danniel

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Posted 24 May 2022 - 04:48 PM

Since a couple of months I am doing this protocol twice a week. I noticed surprising effects on my mental and psychological well-being. During the last month I added a quarter a teaspoon of canabutter to the brownie and my creativity is going through the roof for most of about 6 hours. I plan to replace one time canabutter with a microdose of psilocybin.

 

Did anyone notice mental and psychological effects after following the protocol?

Does my experience make sense or is just placebo?


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#1779 Turnbuckle

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Posted 24 May 2022 - 05:12 PM

Since a couple of months I am doing this protocol twice a week. I noticed surprising effects on my mental and psychological well-being. During the last month I added a quarter a teaspoon of canabutter to the brownie and my creativity is going through the roof for most of about 6 hours. I plan to replace one time canabutter with a microdose of psilocybin.

 

Did anyone notice mental and psychological effects after following the protocol?

Does my experience make sense or is just placebo?

 

A low dose of psilocybin is the right approach --

 

At a biological level, psilocybin induced a dose-dependent effect on neurogenesis, with a low dose increasing, and a high dose decreasing neurogenesis...

:text=At%20a%20biological%20level%2C%20psilocybin,dose%20decreasing%20neurogenesis%20(62)' class='bbc_url' title='External link' rel='nofollow external'>https://www.frontier...urogenesis (62)

 

 

The use of serotonin reuptake inhibitors with C60 and dihydromyricetin will increase neural SC proliferation. If anyone tries it with a small dose of cocaine (a reuptake inhibitor of  dopamine, norepinephrine and serotonin), I would be interested in hearing the results.


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#1780 Seismitoad

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Posted 25 May 2022 - 11:31 PM

TB, this thread is fascinating and I think your philosophy here is sound.  I'm too young to have use for it, however I know someone of a similar age who has very slow wound healing and slow learning despite reasonable intelligence.  I suspect this person has depleted stem cell pools due to early life trauma, both physical and mental.  I'm thinking I'll buy them a couple supplements to try (if it doesn't work I can give the remainder to my dad who can certainly use it).  Would you say this is an appropriate minimal stack?

 

C60

Stearic acid brownie

Dihydromyricetin

 

Also, as a suggestion, it may be useful to list the purpose of each supplement in a future protocol update.  This thread is rather long and it's hard to keep track of what's for what!  



#1781 Turnbuckle

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Posted 26 May 2022 - 02:17 AM

Here is minimum protocol (shown in bold) for those who want to try it out. For the full protocol, see post 1711

 

Brain mito fusion brownie (contains two mito fusion agents). Three hours later —

 

1. C60 dissolved in oil — one teaspoon if in olive oil, 1.5-2 teaspoons if in MCT oil (stem cell activation)

2. Sunflower lecithin — 2-4 grams (choline source and emulsifier)

3. Dihydromyricetin — 2-6 grams (mito fusion agent that crosses BBB)

4. Liposomal glutathione — .5-1 grams (master anti-oxidant)

5. AKG (alpha ketoglutarate) — 1 gram (promotes demethylase, fast acting)

6. AAKG  — 2-3 grams (promotes demethylase, slower acting)

7. SAM-e — 100-500 mg (methyl donor)

8. Lysine — 2-6 grams (stem cell nutrition)

9. Methionine — 1-3 grams (stem cell nutrition)

10. Astragalus root powder — 500 mg (telomerase promoter to prevent telomeric aging of stem cells)

 

Next day (mito fission, may be repeated for 2 days) —

 

1. Nicotinamide — 1 gram (mito fission agent)

2. Ribose — 1-2 grams (improves mito fission when used with nicotinamide)

3. AAKG  — 2-3 grams  (demethylase, slower acting)

4. Lysine — 2-6 grams (stem cell nutrition)

5. Methionine — 1-2 grams (stem cell nutrition)

 

NOTES:

1. Mito fusion + C60 produces stem cell proliferation. Adding demethylase nearly doubles the epigenetic age decline. May be added to fruit juice in a blender.

2. Mito fission promotes apoptosis of senescent cells, which are then replaced with stem cells. With replacement, epigenetic age is reduced.

3. Using too much astragalus will block stem cell replacement.

4. A link to the most recent protocol is always found on my profile page (click on my picture).

 

 

 


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#1782 mbdrinker

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Posted 26 May 2022 - 10:13 PM

I think if it were the case holliwood actors would not age but it's not like that. I don't believe you can increase stem cell number this way. In moscow the so called elite makes injections of stem cells obtained from milling aborted babies in milling machine 20-25 weeeks year old if i remember correctly. Or they take stem cells from bone brains, multiply them in lab and then inject
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#1783 Turnbuckle

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Posted 26 May 2022 - 10:23 PM

I think if it were the case holliwood actors would not age but it's not like that. I don't believe you can increase stem cell number this way. 

 

 

You can believe what you want, of course, but as for Hollywood actors, that makes no sense at all.


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#1784 yz69

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Posted 27 May 2022 - 03:08 AM

Hi TB, I noticed that you removed curcumin from the fission protocol, why? 


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#1785 Kentavr

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Posted 27 May 2022 - 08:12 AM

I think if it were the case holliwood actors would not age but it's not like that. I don't believe you can increase stem cell number this way. In moscow the so called elite makes injections of stem cells obtained from milling aborted babies in milling machine 20-25 weeeks year old if i remember correctly. Or they take stem cells from bone brains, multiply them in lab and then inject

 

You're wrong. I live in Moscow. If there was such a thing, it was unofficial.
 
It may have been done before, about 15 years ago (and it certainly could have been done not only in Russia, but also in the United States), but it's not the case now.
 
After the wave of cancer cases among showbiz people across the country, rich people realized that the risks far outweighed the benefits. After all, any stem cell in someone else's body is capable of becoming a cancer cell and starting to reproduce aggressively. But there have been such results all over the world. A lot of world celebrities, not only in Russia, have used such methods of rejuvenation. Such methods of rejuvenation were also used in the United States, simply for this procedure clinics from the United States were registered in neutral countries, and patients traveled there. But in fact it was the same as in Russia.
 
Now in Moscow peptide treatments, gentle versions of Botox, lymphatic drainage and sports exercises and correct nutrition are much more popular. And believe me, many of those who maintain a toned body look at 50 years old as if they were 30.
 
I'm very surprised that negative information is still being spread about my country. Please don't believe everything they write on the fence, let alone what your politicians say (vodka, balalaika, hat with earflaps, etc.). This is a lie. Our country has a huge scientific potential, which finds its application in the form of ready-made technological solutions. 
 
I, for example, have greatly reduced my pulse pressure by using the right combination of drugs and dietary supplements. And this, by the way, is a significant risk factor for mortality and neurodegenerative diseases. In fact, if your pulse pressure is above 50, your own body starts killing itself, damaging your organs. The pulse pressure begins to tear them from the inside, structural changes begin, which you can't cure with simple supplements and protocols. And that greatly increases the risk of mortality in people over the age of 80. 
 
At 90-100 years of age, even if you have renewed your stem cells, the extracellular matrix gives you a death sentence. Imagine your blood vessels and all of your body organs being pulled together by "strands of steel" that you can only see under a microscope. These are glucosepane cross-links.
 
Imagine that your blood vessels and all the organs of your body are pulled together by "threads of steel," which are pulling you tighter and tighter every year. At 60 it is not very noticeable, at 70 it begins to bother you, at 80 it already affects your mobility, and at 90 it just squeezes you so tightly that your chances of living to be 100 are almost minimal. And, in the vast majority of cases, it's the extracellular matrix that's causing mortality after age 90.
 
And you can't be saved by simply renewing your stem cells, you need to increase the elasticity of your blood vessels. 
 
This is physics; ordinary stem cells won't help here. Rejuvenation is a complex approach.
 
Stem cell renewal protocol won't help you here. Turnbuckle still has a high pulse pressure despite the protocol. You can have a very good stem cell pool and suddenly pass away from a stroke. You need both stem cells and an elastic extracellular matrix.
 
I was able to get my pulse pressure down dramatically from 45-46 to 32-34 in about 1.5 months. It is also a kind of achievement, as good as this protocol.

Edited by Kentavr, 27 May 2022 - 08:31 AM.

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#1786 QuestforLife

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Posted 27 May 2022 - 08:36 AM

Our country has a huge scientific potential, which finds its application in the form of ready-made technological solutions.

I, for example, have greatly reduced my pulse pressure by using the right combination of drugs and dietary supplements. And this, by the way, is a significant risk factor for mortality and neurodegenerative diseases. In fact, if your pulse pressure is above 50, your own body starts killing itself, damaging your organs. The pulse pressure begins to tear them from the inside, structural changes begin, which you can't cure with simple supplements and protocols. And that greatly increases the risk of mortality in people over the age of 80.

At 90-100 years of age, even if you have renewed your stem cells, the extracellular matrix gives you a death sentence. Imagine your blood vessels and all of your body organs being pulled together by "strands of steel" that you can only see under a microscope. These are glucosepane cross-links. And you can't be saved by simply renewing your stem cells, you need to increase the elasticity of your blood vessels.

This is physics; ordinary stem cells won't help here. Rejuvenation is a complex approach.

Stem cell renewal protocol won't help you here. Turnbuckle still has a high pulse pressure despite the protocol. You can have a very good stem cell pool and suddenly pass away from a stroke. You need both stem cells and an elastic extracellular matrix.

I was able to get my pulse pressure down dramatically from 45-46 to 32-34 in about 1.5 months. It is also a kind of achievement, as good as this protocol.


I'd agree that Russia has a great scientific heritage. Western disregard for peptides, and epitalon in particular, is ridiculous.

But your argument on pulse pressure makes little sense. The difference between systolic and diastolic pressure is informative, but saying the absolute difference is all that matters is silly. For example pulse pressure > 60 is a risk factor for CVD in the elderly, and <40 is a warning sign of cardiac output failure. But clearly these are contingent on other things.

For example having a blood pressure of 120/60 is healthy at any age. Just because the pp is 60 means nothing. 140/80 also has pp of 60 but this is not so good. 160/100 has a pp of 60 and this is now dangerous.

The extra cellular matrix and stem cells are not entirely independent. Hence why a statin and sartan combo ( DOI: 10.3892/etm.2015.2622 )improves markers of arterial health (PWV, FMD, etc) and they work by increasing endothelial progenitors, which then repair the arteries.
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#1787 Kentavr

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Posted 27 May 2022 - 09:06 AM

I'd agree that Russia has a great scientific heritage. Western disregard for peptides, and epitalon in particular, is ridiculous.

But your argument on pulse pressure makes little sense. The difference between systolic and diastolic pressure is informative, but saying the absolute difference is all that matters is silly. For example pulse pressure > 60 is a risk factor for CVD in the elderly, and <40 is a warning sign of cardiac output failure. But clearly these are contingent on other things.

For example having a blood pressure of 120/60 is healthy at any age. Just because the pp is 60 means nothing. 140/80 also has pp of 60 but this is not so good. 160/100 has a pp of 60 and this is now dangerous.

The extra cellular matrix and stem cells are not entirely independent. Hence why a statin and sartan combo ( DOI: 10.3892/etm.2015.2622 )improves markers of arterial health (PWV, FMD, etc) and they work by increasing endothelial progenitors, which then repair the arteries.

 

Yes, it's all true, but up to a certain point. After 90-100 years, the intercellular space decreases so much that cells practically stop dividing: there are numerous cross-links of glucosepane with collagen in the surrounding space, as well as cross-links in elastin. 
 
Because of the large number of cross-links, even cancerous tumors stop proliferating: they simply cannot physically overcome the barrier of glucosepan cross-links! This is one of the reasons, I believe, why there is a so-called "mortality plateau" after 100 years of age, because the number of cancers decreases dramatically. 
 
Yes, and you correctly said that the extracellular matrix and stem cells are not completely independent. Nevertheless, I very much doubt that stem cells will be able to do anything after age 90 if all niches are squeezed due to cross-linking.
 
Measures to increase matrix elasticity should be taken as early as possible. Four ways come to my mind:
 
1. Increasing the production of elastin components
2. Increasing the production of your own hyaluronic acid
3. Reducing overall inflammation in the body (e.g., by taking 25-40 mg of doxycycline).
4. Reduction of extracellular matrix calcination (due to complexing agents such as IP6).
 
The third method is necessary because severe inflammation in the aging body increases the production of metallomatrix proteinases, which begin to destroy collagen and elastin. This is a "double-edged sword": on the one hand, we need it for tissue change, but on the other hand, because aging tissue contains many glucosepane cross-links, the body cannot remove the products of destruction, and extracellular matrix "becomes as fluffy as a dandelion" and collagen takes the place of elastin, which further tightens the matrix.
 
Because of this effect a lot of cross-links are formed between separate bundles of fibers, and as a result in 90-100 years no stem cells can help to recover from a stroke, because they will not be able to do it. They simply will not leave their niche. 
 
It is better for the cross-links to accumulate inside the fiber bundles, and for the tissue to have enough elastin and collagen. 
 
We need to combine two approaches: on the "life" side (stem cells) and on the "structure" side (extracellular matrix). I consider this approach to be more holistic.

Edited by Kentavr, 27 May 2022 - 09:22 AM.

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#1788 mbdrinker

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Posted 30 May 2022 - 01:05 AM

I think Botox is a cosmetic crap and not a rejuvenator. Look at botoxed putin. He looks like a funny хомяк. Or his legs are dancing definitely from amphetamins or cocaine. I bet he has a dwarf’s penis, tiny as a nail. That’s why he has chosen Asian kabajeva since they have tiny vaginas. However Putin himself contradicts your optimistic views on rejuvenation. All of them gurchenko, jirinovski, etc, David rokfeller , money did not help them. My grandgrandgrandgrandfather lived 104 years being a simple peasant in Siberia. But I agree that inflammation adds much to aging. I will publish a post in another topic now how I have managed to weaken arthritis without nonsteroid anti inflammation drugs. Slav tribes have different genetics. Some live longer and look younger than others in spite of general misconception that Slavs become old too early. But your theory on increasing elasticity is interesting and seems grounded. But I would chose some ephtanasia instead of long life as an old man, there is a religious chance to be born in another body and even better planet without those filthy rich thieves and their servants
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#1789 mbdrinker

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Posted 30 May 2022 - 01:21 AM

By the way where have you found the info that doxycycline extends life? I have read its description. It seems to kill bacteria instead of inhibiting generation of prostaglandins... I would be interested in something anti inflammatory to defeat arthritis but without bad effects on stomach and hearing as nsaids.
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#1790 Kentavr

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Posted 30 May 2022 - 11:18 AM

I think Botox is a cosmetic crap and not a rejuvenator. Look at botoxed putin. He looks like a funny хомяк. Or his legs are dancing definitely from amphetamins or cocaine. I bet he has a dwarf’s penis, tiny as a nail. That’s why he has chosen Asian kabajeva since they have tiny vaginas. However Putin himself contradicts your optimistic views on rejuvenation. All of them gurchenko, jirinovski, etc, David rokfeller , money did not help them. My grandgrandgrandgrandfather lived 104 years being a simple peasant in Siberia. But I agree that inflammation adds much to aging. I will publish a post in another topic now how I have managed to weaken arthritis without nonsteroid anti inflammation drugs. Slav tribes have different genetics. Some live longer and look younger than others in spite of general misconception that Slavs become old too early. But your theory on increasing elasticity is interesting and seems grounded. But I would chose some ephtanasia instead of long life as an old man, there is a religious chance to be born in another body and even better planet without those filthy rich thieves and their servants

 

Let's leave politics out of this discussion thread. 
 
Although, in my opinion, much more dangerous to humanity are the satanists, who print their symbols on the U.S. dollar, organize color revolutions, and impose rules on everyone on how to live.
I ask you not to forget that the first revolutionary in history is satan.
 
Let's talk about what really matters to ordinary people. 
 
Elasticity theory is not my theory. It has existed for quite a long time. It is actively developed by Dmitry Veremeenko. He is a biohacker from Russia. 
 
He also develops methods of effective life prolongation that work on people. At the same time he is very conservative in his approach, uses only strict scientific evaluation, while screening out many falsified scientific studies, as well as studies that do not have good reliability.
 
Here is his website:
 

 

Using the data from this site, as well as my own research and speculation, I was able to put together a protocol that effectively increases vascular elasticity.
 
The effects after using the protocol are stable (my pulse pressure remained stable even after the protocol was discontinued. It's been 4 months now, and my pulse pressure hasn't increased.).
 
I wrote my protocol in this thread (see post https://www.longecit...-56#entry914319

 

By the way where have you found the info that doxycycline extends life? I have read its description. It seems to kill bacteria instead of inhibiting generation of prostaglandins... I would be interested in something anti inflammatory to defeat arthritis but without bad effects on stomach and hearing as nsaids.

 

That's my guess. I have consulted with leading developers in the field of gerontology in Russia, and they also agree that this is one of the most correct approaches to the extracellular matrix that there can be.

 

You can also read this information: https://nestarenie.r...vaet-zhizn.html

 

Doxycycline up to 50 mg per day is safe enough and does not affect the human microflora.

 

I take 33 mg per day (1/3 of a tablet).


Edited by Kentavr, 30 May 2022 - 11:25 AM.

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#1791 Empiricus

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Posted 30 May 2022 - 01:46 PM

I just got my second TruMe report back.

 

First test date 2021-08-04

Biological age: 40.7 years

Chronological age: 57.5 years

Delta: 16.8 years

 

Second test date 2022-03-06

Biological age: 37.8 years

Chronological age: 58.1 years

Delta: 20.3 years

 

I started the stem cell protocol rounds on 2020-09-04. I did 11 rounds before my first test and 8 rounds between the 1st and 2nd tests. I kept up with the protocol updates along the way.

 

 

Have you observed improvements in your health or fitness level during this period that could be attributed to the protocol?  Have others noticed anything different about you? 


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#1792 Turnbuckle

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Posted 30 May 2022 - 02:15 PM

Have you observed improvements in your health or fitness level during this period that could be attributed to the protocol?  Have others noticed anything different about you? 

 

Yes and yes. This has been asked and answered several times over the past few years. Epigenetic age testing was developed to correspond to chronological age, and is a better predictor of biological age than chronological age. So a rollback of epigenetic age with this method is a rollback of biological age. There are limitations, as this method can only restore stem cell pools where there are stem cells to proliferate, and stem cells are useless if there are no target cells to be replaced. So it cannot bring back hair where the root no longer exist, it can't bring back hair color if the root has no functional melanocytes, and it can't cure diabetes if the β-cells are all gone. Likewise, much of the brain cannot replace the loss of neural cells, but some can, such as the hippocampus. Thus your memory can be improved if you use components that can penetrate the BBB, though this improvement does not show up in any epigenetic test.


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#1793 mbdrinker

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Posted 30 May 2022 - 08:40 PM

Thanks for info. Is that veremeenko the guy Dmitry who created bessmertie.ru in early 00s? That guy was promoting some harmful substances like dmae causing skin apoptosis. Are you sure you can trust another immortality wizard who is so generous to extend our lives while ongoing wars and various kavid projects aim to cut down population. It,s tempting to be immortal but you know the Satan always uses temptation to its benefit. Also why does doxycycline instruction not have any mentioning of its anti-inflammatory effects. Aspirin is mild nsaid which is a known fact. Kardiomagnil is usual aspirin sold several times costlier. Drugstores in Russia sell some fake ascorbic acid, you can check it by trying to turn methylene blue into leico mb form. It,s disgusting. Fake melatonin too and perhaps hundreds of other names.
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#1794 mbdrinker

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Posted 30 May 2022 - 09:24 PM

Your veremeenko is promoting metformin as #1 life extender. I suggest your watching doctor Petrik on youtube where he criticizes this metformin with justifications. Instead of lengthening grey life by debatable chemicals from debatable promoters I suspect that psychedelic experience can make your short life much more exciting and fruitful.
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#1795 Kentavr

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Posted 31 May 2022 - 11:12 AM

Your veremeenko is promoting metformin as #1 life extender. I suggest your watching doctor Petrik on youtube where he criticizes this metformin with justifications. Instead of lengthening grey life by debatable chemicals from debatable promoters I suspect that psychedelic experience can make your short life much more exciting and fruitful.

 

We all make mistakes. And Dmitri Veremeenko also used to make mistakes while his professional competence was growing. This is normal. He published a lot of articles before 2018, which were very interesting, but there were fundamental mistakes: the role of the extracellular matrix in the aging process was not taken into account. 
 
You can read his article, it is currently the best article on the influence of the extracellular matrix on aging:
 
 
And that's a fact. The matrix will squeeze you, crush you, and the pulse wave will destroy your organs if you don't pay attention to the elasticity of the extracellular matrix.
 
Here, in this thread, I argue that simply renewing stem cells to prolong life is not enough, and I call for combining approaches. You need both a therapy to increase your own stem cell pool and to increase the elasticity of the extracellular matrix. 
 
Dmitry Veremeenko quote:
 
"Components of the extracellular matrix serve as activators for receptors on the cell surface that trigger signaling cascades. If all of them are completely removed, the cell self-destructs. The key receptors interacting with the extracellular matrix are mechano-sensitive integrins.
They are involved in intercellular interactions and wound healing, as well as in degenerative cartilage diseases, fibrosis, and cancer [pubmed.ncbi.nlm.nih.gov/29510460]
 
Generally speaking, the extracellular dictates the fate of cells entirely. The extracellular matrix controls cell differentiation [ncbi.nlm.nih.gov/pmc/articles/PMC5866410] (including through stiffness). The more water and less collagen, the softer the tissue and the softer the extracellular matrix, and the cells of this tissue differentiate into cells for this tissue. The same results have been reproduced with gels of different stiffness. That is, the extracellular decides whether a stem cell will differentiate into nerve cell, bone cell, muscle cell, etc. through stiffness signals."
 
Improving the elasticity of the extracellular matrix will also help Turnbuckle further reduce his epigenetic age. 
 
If we view aging as a gradual increase in the risk of mortality with age, reducing epigenetic age is not a sufficient measure for this.
 
In other words, if you have left ventricular hypertrophy due to a high pulse wave that has developed into heart failure, what difference does it make to the fact that your cells have an epigenetic age of 30 years less if you will die in a few years anyway???
 
The protocol that Turnbuckle is developing is very good, wonderful! But this method alone is not enough.
 
Here I am simply suggesting that we combine the approaches to make the life extension methodology a more holistic approach and get rid of the illusions.
 

 


Edited by Kentavr, 31 May 2022 - 11:39 AM.

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#1796 Turnbuckle

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Posted 31 May 2022 - 06:29 PM

 

 
 
If we view aging as a gradual increase in the risk of mortality with age, reducing epigenetic age is not a sufficient measure for this.
 
 

 

 

That's a circular argument. Better to ask: does mortality risk depend on chronological age or epigenetic age? I think the latter. And there's evidence for it --

 

the difference between a person’s epigenetic age and chronological age predicted his or her risk of mortality, independent of known mortality risk factors. 

https://www.nia.nih....dicts-mortality

 

 

As for the extracellular matrix, that is not static, but is constantly being remodeled. And central to that remodeling is the availability of stem cells. The paper you referenced says this --

 

There is a hypothesis that regeneration is probably turned off in an adult organism, since an adult animal needs to quickly, albeit poorly to heal wounds. Probably, regeneration is turned off due to an increase in the rigidity of the matrix in an adult organism, since survival depends on the rate of wound recovery.

 

 

This is one hypothesis piled on top of another. In my view, if regeneration is turned off, it's due to the exponential decline in viable stem cell numbers. Restore them by forcing SC proliferation, and you restore regeneration. 


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#1797 Kentavr

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Posted 31 May 2022 - 08:26 PM

This is one hypothesis piled on top of another. In my view, if regeneration is turned off, it's due to the exponential decline in viable stem cell numbers. Restore them by forcing SC proliferation, and you restore regeneration. 

 

1. You cannot remodel the extracellular matrix if it is too strongly cross-linked with glucosepane cross-links. The matrix just becomes "like a dandelion", the degradation products do not leave the place of destruction, because the detachment of degradation products does not happen until the end. Look at the links above.
2. If your niches where the stem cells sit cannot leave it, you are doomed.
 
Also: 
Your pulse pressure is still high, which means that there is a structural change in the body that can impair the function of all organs and tissues.
 
I also assume that you do not have a further decrease in epigenetic age, because you have reached the limit of the stem cells' ability to decrease epigenetic age. But you haven't been dealing with the matrix. Integrins affect the activity of genes in cells, and they affect all systems of the body very strongly, increasing the epigenetic age. 
 
I assume that if you reduce the rigidity of the extracellular matrix, you will have a synergistic effect: your age will decrease even more: I assume even more than if you continue to use your default protocol. 

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#1798 mbdrinker

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Posted 31 May 2022 - 09:08 PM

Kentavr спасибо Комрад за ссылку. I have always had suspicion that resveratrol is hype and lies and your link proves it. The same about nnm. By the way doctor petrik is a victim of nnm propaganda. I personally believe there are no powerful life extenders as my gran...pa lived 104 without them and rich jirinovski 72... there is also an exciting fact that some people are sick for 40-50 years and live long and others are healthy and sportive but momentarily die from heart attack at about 50.
That’s why I entrust my longevity to higher forces. I myself just want more psychedelic stuff to encolor my life. As they joke 5 mg of amph boost your mood, 10 make you enjoy a picture for hours and 50mg will turn you into a pilot of a spacecraft. If you know anything from Russian drugstores which improves mood like mb please let us know
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#1799 Turnbuckle

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Posted 31 May 2022 - 09:29 PM

 

 
I assume that if you reduce the rigidity of the extracellular matrix, you will have a synergistic effect: your age will decrease even more: I assume even more than if you continue to use your default protocol. 

 

 

 

Epigenetic age reduction occurs when you replace telomerically aged out cells (that are also epigenetically old) with new somatic cells that derive from stem cells with near zero age. You can't reverse epigenetic age past a certain point because cells first have to age out and commit suicide to be replaced, and thus the best you can achieve will have a mixed population of ages. As for the extracellular matrix, if it is being properly and continuously remodeled, then crosslinks will get recycled. If the body gets behind on maintenance and it reaches a certain level of crosslinks, then I expect you might have a problem. But I don't think this is central to aging. It doesn't explain findings like this --

 

About 5 percent of adults aged substantially faster than others (i.e., epigenetic age was more than 10 years older than chronological age), leading to a nearly 50 percent increased risk of death.
 
The results were adjusted for mortality-related risk factors, including smoking, obesity, and health conditions such as cancer, high blood pressure, and diabetes. The associations also held across sex and racial groups, as the analysis encompassed data from 13,089 non-Hispanic whites, Hispanics, and blacks.
https://www.nia.nih....dicts-mortality (the previously linked paper)
 

 

 

Nor do I understand how the reduced elasticity of the extracellular matrix might prevent replacement of aged out cells. Can you point to actual evidence of this? I can imagine that a person with a lot of crosslinking due to smoking or alcohol abuse might also have depleted stem cell niches. But that would be a correlation, not a causation.

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#1800 Kelvin

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Posted 31 May 2022 - 09:48 PM

Could the C60 protocol benefit parts of the brain like the frontal lobes which apparently cannot regenerate neurons by boosting the circulation of stem cells from nearby areas that have them in abundance such as the hippocampus?

 

Might stem cell circulation be promoted by taking something like lithium at the same time as the C60 + fusion part of the protocol? (assuming no negative interactions between lithium and C60, otherwise another supplement would be needed)

 

Perhaps if they had broader circulation across the brain, and if brain trauma is not excessive, they could find target cells in the frontal lobes and begin regenerating neurons.

 

If that could be done the main risk would be that unhealthy stem cells populate niches where they might do more harm than good.  But this risk could be mitigated by only adding lithium for a couple cycles every year, or few years, considering how long-lived neurons are.


Edited by Kelvin, 31 May 2022 - 09:53 PM.

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