2503 replies to this topic

[NeilR]

I have stated several times that this geriatric protocol is experimental. It is for refilling your stem cell niches and using that to reverse epigenetic age, so unless you have reason to believe that your stem cells are depleted, or that stem cell numbers need to be enhanced for a specific purpose (injury or surgery or the like), or that your epigenetic age is increasing too rapidly, using this protocol is not recommended. After building up my own stem cell pools, I have continued stimulating stem cells at appropriate times without C60. I use 10 grams each of threonine and leucine after senyloic treatment, for instance, or prior to exercise. Pluripotent stem cells have a critical need for threonine and muscle satellite cells are triggered by leucine.*

As for your N+R stack, this is off topic on this thread. My N+R protocol was directed to eliminating dysfunctional mitochondria, but someone 30 years old is unlikely to have any. I suggest you get your genetics tested, and if you have one or more APOE4 genes, then there might be a reason to take nicotinamide.

*The effect of leucine on muscle gain has been known for some time. It operates by increasing satellite cells, which then mature into muscle cells. The discovery that mice and human pluripotent cells are so dependent on threonine is very new. Even the presence of pluripotent cells in the adult is new and not totally accepted. That said, threonine supplementation is not recommended for daily use, but only as part of this protocol. Don't feed your stem cells when they don't need feeding.

Thank you for the detailed response Turnbuckle. So then what should I take to at least keep my stem cells from depleting? I assume that you don’t recommend Thearine based on this comment. Would taking Icaarin, Taurine and TUDCA make sense? I do plan to test my epigenetic age. I tested my telomeres and was told that I‘m two years younger than my current age, but unfortunately I didn’t take any tests before beginning my telomere treatments, so I don’t know if this means that my epigenetic age has been sped up or if the treatments didn’t affect my telomere age and those treatments had nothing to do with it.

Edited by NeilR, 15 January 2019 - 06:37 AM.

[NeilR]

I think Niacin and Resveratrol are contraindicated. One will block Sirt2. One will activate it.

I assume you mean that Resveratrol will block it? Thank you for letting me know.

Edited by NeilR, 15 January 2019 - 06:37 AM.

[QuestforLife]

That test doesn't measure telomere length ...

That's the point, it's a methylation test. And in this anecdotal example, of a person known to use telomerase activators for 10 years, he was found to have a young (-7yr) epigenetic age. Which doesn't fit the theory. So maybe telomerase activators are more effective in progenitor cells. We don't know. Up to speed now?

[Turnbuckle]

That's the point, it's a methylation test. And in this anecdotal example, of a person known to use telomerase activators for 10 years, he was found to have a young (-7yr) epigenetic age. Which doesn't fit the theory. So maybe telomerase activators are more effective in progenitor cells. We don't know. Up to speed now?

 

 

What anecdotal example? Do you have a link to it? Because if this person is Dr Ed Parks, he's a vendor of telomerase activators. He's not going to undercut his business.

[QuestforLife]

What anecdotal example? Do you have a link to it? Because if this person is Dr Ed Parks, he's a vendor of telomerase activators. He's not going to undercut his business.

 

Yes, I posted the link upthread.

 

I did say it's only 1 anecdote. And yes, Dr Park is not a disinterested party. But still.  Do you have any counter examples of where telomerase activators HAVE caused an older epigenetic age, and if so, have they actually caused faster aging (i.e. worse health outcomes)?

[Turnbuckle]

Yes, I posted the link upthread.

 

I did say it's only 1 anecdote. And yes, Dr Park is not a disinterested party. But still.  Do you have any counter examples of where telomerase activators HAVE caused an older epigenetic age, and if so, have they actually caused faster aging (i.e. worse health outcomes)?

 

 

I don't see that example in your link. Could you post it here? (But if the claim has only one epigenetic test data point, it is worthless for this argument.)

 

Telomerase activators do not cause cells to become epigenetically older, they allow them to become older by extending their lifespans. An in vitro study--

 

...observations from these experiments do not support the proposition that hTERT stimulates epigenetic ageing. Instead, by causing cells to bypass replicative senescence, hTERT allows the inherent process of epigenetic ageing, which occurs regardless of its presence, to continue. Put simply, while hTERT may appear on the surface, to exacerbate the epigenetic ageing of cells, in truth hTERT, by preventing telomere attrition, prolonged the lifespan of the cells, allowing them growing older (as measured by the epigenetic clocks).

https://www.aging-us...cle/101588/text

 

[lost69]

Yes, I posted the link upthread.

 

I did say it's only 1 anecdote. And yes, Dr Park is not a disinterested party. But still.  Do you have any counter examples of where telomerase activators HAVE caused an older epigenetic age, and if so, have they actually caused faster aging (i.e. worse health outcomes)?

 

i think one test only is totally meaningless, my first zymo dna test was -8 few months into c60/gdf11 use.so probably so low naturally or due to healthy diet

[QuestforLife]

https://www.recharge...s-your-dna-age/

 

Here you go Turnbuckle, and yes it's just one data point. We need more data from longecity members to prove or disprove the inverse relationship between telomere length and methylation. I'm well aware of the argument and the you paper you posted; I've already stated my reasons why I believe it may not be translated in vivo - but we'll see. If we manage to increase stem cell numbers as a percentage of total cells then hopefully we can both increase telomeres and decrease epigenetic age (assuming that is a real 'thing' that is separate from cell type).

[QuestforLife]

i think one test only is totally meaningless, my first zymo dna test was -8 few months into c60/gdf11 use.so probably so low naturally or due to healthy diet

 

Great result, pity you're not part of the longecity project where we all share our results.

 

Would you attribute your lower epigenetic age to the stearic acid/C60, or have you been on any other long term medications or supplements?

Edited by QuestforLife, 15 January 2019 - 01:56 PM.

[lost69]

Great result, pity you're not part of the longecity project where we all share our results.

 

Would you attribute your lower epigenetic age to the stearic acid/C60, or have you been on any other long term medications or supplements?

 

 no stearic acid at that time, it was 2017, and c60 was from vendors later found fraud....i think it is due to my family genes, many reaching close to 100yo in good health both in my mother and father's family

Edited by lost69, 15 January 2019 - 02:34 PM.

[Turnbuckle]

Here you go Turnbuckle, and yes it's just one data point. We need more data from longecity members to prove or disprove the inverse relationship between telomere length and methylation. I'm well aware of the argument and the you paper you posted; I've already stated my reasons why I believe it may not be translated in vivo - but we'll see. If we manage to increase stem cell numbers as a percentage of total cells then hopefully we can both increase telomeres and decrease epigenetic age (assuming that is a real 'thing' that is separate from cell type).

 

So it's meaningless. In any case, I don't need it proved or disproved. It's already clear from the in vitro data, and there's no logical reason to believe that lengthening telomeres could possibly reverse epigenetic aging. As discussed above, it will have no epigenetic effect at all except to lengthen the potential extent of aging.

 

By preventing cellular senescence, telomere lengthening will certainly improve your health over the short term and may increase your lifespan (assuming you don't get cancer from it), but for age reversal, stem cell pool expansion + senolytics is the way to go, IMO. Filling stem cell pools by itself only gets you so far. They also need signals that come from dying cells--Apoptosis-induced proliferation functions as a core for organ regeneration, and they won't get those signals if cells are rescued and don't die. 

[QuestforLife]

By preventing cellular senescence, telomere lengthening will certainly improve your health over the short term and may increase your lifespan (assuming you don't get cancer from it), but for age reversal, stem cell pool expansion + senolytics is the way to go, IMO. Filling stem cell pools by itself only gets you so far. They also need signals that come from dying cells--Apoptosis-induced proliferation functions as a core for organ regeneration, and they won't get those signals if cells are rescued and don't die. 

 

I agree that even with long telomeres DNA maintenance isn't perfect, so cell replacement from a stem cell niche is preferable when possible. But we might yet find telomerase preferentially helps stem cells in vivo. There is evidence to support this.

 

And on apoptosis; did you know that apoptosis signaling may also include telomerase?

 

See Fig 2, here:

 

https://www.ncbi.nlm...pubmed/22189618

[Turnbuckle]

And on apoptosis; did you know that apoptosis signaling may also include telomerase?

 

See Fig 2, here:

 

https://www.ncbi.nlm...pubmed/22189618

 

Your link doesn't even mention apoptosis.

[lost69]

turnbuckle

i'm stillusing the old protocol update 2 with c60 which has no leucine.can i add 5g leucine to "5g theronine and 5g taurine"?also plan to use 5g leucine 5g theronine post swimming later same day before bed

 

using 60mg lansoprazole for laryngitis due to acid refulx/sibo for 3 months and also less carbo on diet  stopped many benefits from this protocol and made weight loss/muscle loss, now i stopped lansoprazole and plan to not take it ever again and i was thinking leucine would be the best for fast muscles mass recovery

   

 

Edited by lost69, 15 January 2019 - 03:13 PM.

[QuestforLife]

Your link doesn't even mention apoptosis.

 

My mistake, it's the senescent feeder cells that provide the telomerase (or most of it).

 

This paper spells it out more clearly.

 

https://ajp.amjpatho...0594-4/fulltext

 

In any case, senolytics probably is very useful if done at the right time.

[QuestforLife]

Regarding the Horvath telomere paper you posted Turnbuckle (https://www.aging-us...cle/101588/text), we might need to take account of the following when testing our interventions on epigenetic age:

 

the new skin & blood clock can form the basis of an assay to test for such interventions. This clock out-performs the pan-tissue clock which is already highly accurate for most tissues and cells in the body, but for unknown reasons exhibit a considerable age off-set when used on some cells cultured in vitro. Furthermore, the pan tissue clock also differed substantially from the skin & blood clock when applied to adult human coronary artery cells: unlike the skin & blood clock, it led to a substantial offset and did not reveal the increase of epigenetic age in function of cell growth. We have at present, no explanation for this curious observation

 

It may well be that the current MyDNAge test is not suitable for the changes expected in saliva or blood.

Edited by QuestforLife, 15 January 2019 - 03:42 PM.

[NeilR]

So it's meaningless. In any case, I don't need it proved or disproved. It's already clear from the in vitro data, and there's no logical reason to believe that lengthening telomeres could possibly reverse epigenetic aging. As discussed above, it will have no epigenetic effect at all except to lengthen the potential extent of aging.

By preventing cellular senescence, telomere lengthening will certainly improve your health over the short term and may increase your lifespan (assuming you don't get cancer from it), but for age reversal, stem cell pool expansion + senolytics is the way to go, IMO. Filling stem cell pools by itself only gets you so far. They also need signals that come from dying cells--Apoptosis-induced proliferation functions as a core for organ regeneration, and they won't get those signals if cells are rescued and don't die.

So what should a younger person do in order to do that? I assume your senolytics protocol and some type of stem cell maintenance? So something like Icariin, TUDCA, Taurine but without c60 since you say it’s not for younger people?

[Turnbuckle]

The latest stem cell protocol can be found in post #694, and a link to the latest can always be found on my profile page. The following mostly-flavonoid senolytic protocol seems to work fairly well, at least when one has topped off their stem cell pools. It is experimental, of course.

 

Senolytic protocol with stem cell replacement

This is where epigenetically old senescent cells are removed and replaced with epigenetically young cells derived from stem cells

 

Time 0 —

Curcumin (phytosome or liposome) — 2 g

Quercetin (phytosome or liposome) — 1 g

Apigenin — 100 mg

Resveratrol — 100 mg

Sodium butyrate — 1 g (then every ½ to 1 hour for 4 hours)

   

Time 4:00 —

Leucine — 5-10 g

Threonine — 10 g

 

 

I’ve also tried adding a gram of azithromycin at one or two hours, and that increases the effect somewhat. The butyrate (p38 activator) seems to make the biggest difference, but must be dosed several times as its half life is just a matter of minutes.

 

I’m working with the hypothesis that stem cells will be mobilized by apoptosis, thus the leucine (which stimulates satellite cells) and threonine (pluripotent cell nutrient).

[lost69]

The latest stem cell protocol can be found in post #694, and a link to the latest can always be found on my profile page. The following mostly-flavonoid senolytic protocol seems to work fairly well, at least when one has topped off their stem cell pools. It is experimental, of course.

 

Senolytic protocol with stem cell replacement

This is where epigenetically old senescent cells are removed and replaced with epigenetically young cells derived from stem cells

 

Time 0 —

Curcumin (phytosome or liposome) — 2 g

Quercetin (phytosome or liposome) — 1 g

Apigenin — 100 mg

Resveratrol — 100 mg

Sodium butyrate — 1 g (then every ½ to 1 hour for 4 hours)

   

Time 4:00 —

Leucine — 5-10 g

Threonine — 10 g

 

 

I’ve also tried adding a gram of azithromycin at one or two hours, and that increases the effect somewhat. The butyrate (p38 activator) seems to make the biggest difference, but must be dosed several times as its half life is just a matter of minutes.

 

I’m working with the hypothesis that stem cells will be mobilized by apoptosis, thus the leucine (which stimulates satellite cells) and threonine (pluripotent cell nutrient).

 

thank you very much, i still get incredible results swimming by high dose C60 so i prefer keeping the old updated 2 protocol unless C60 can be added to this new protocol somewhere

 

in case C60 has no place in this protocol, can i use 10g leucine on both stemcell renewal days and senolytic days?

[Turnbuckle]

thank you very much, i still get incredible results swimming by high dose C60 so i prefer keeping the old updated 2 protocol unless C60 can be added to this new protocol somewhere

 

in case C60 has no place in this protocol, can i use 10g leucine on both stemcell renewal days and senolytic days?

 

See where I linked to post 694? That's the stem cell self-renewal protocol. This flavonoid protocol is for eliminating old cells and replacing them. I prefer not to use C60 here, believing it is best for stem cells to use the signal they're getting from apoptosis for asymmetrical differentiation (vs symmetrical proliferation for building up the pools). This replacement takes place in a state of mito fission, not fusion.

Edited by Turnbuckle, 15 January 2019 - 10:45 PM.

[jabowery]

...

Sodium butyrate — 1 g (then every ½ to 1 hour for 4 hours)

... butyrate (p38 activator) seems to make the biggest difference, but must be dosed several times as its half life is just a matter of minutes...

Is there a significant advantage of Sodium butyrate over equivalent weight Ca/Mg butyrate?  This is one of the more costly items and it seems there is a big price difference.

[lost69]

See where I linked to post 694? That's the stem cell self-renewal protocol. This flavonoid protocol is for eliminating old cells and replacing them. I prefer not to use C60 here, believing it is best for stem cells to use the signal they're getting from apoptosis for asymmetrical differentiation (vs symmetrical proliferation for building up the pools). This replacement takes place in a state of mito fission, not fusion.

 

ok, i had forgotten the need of fission state for max senoltic effect.i ll try this in the future without c60.thank you very much

[Turnbuckle]

Is there a significant advantage of Sodium butyrate over equivalent weight Ca/Mg butyrate?  This is one of the more costly items and it seems there is a big price difference.

 

The price difference is between brands.

[Graviton]

See where I linked to post 694? That's the stem cell self-renewal protocol. This flavonoid protocol is for eliminating old cells and replacing them. I prefer not to use C60 here, believing it is best for stem cells to use the signal they're getting from apoptosis for asymmetrical differentiation (vs symmetrical proliferation for building up the pools). This replacement takes place in a state of mito fission, not fusion.

It is uncertain why you call "flavonoid protocol" as a fission protocol.

Fission state does not seem to be globally caused by flavonoids.

It seems that it is more likely to be a matter of regulation, rather than in one direction.

 

 

https://www.ncbi.nlm...pubmed/28235489

 

 

We investigated RES's effects on mitochondrial network morphology in several cell lines using a quantitative approach to measure the extent of network fusion.

 

 

https://www.ncbi.nlm...les/PMC5256118/

 

 

In contrast, curcumin enhanced mitochondrial fusion activity and reduced fission machinery, and increased biogenesis and synaptic proteins.

[Turnbuckle]

It is uncertain why you call "flavonoid protocol" as a fission protocol.

Fission state does not seem to be globally caused by flavonoids.

It seems that it is more likely to be a matter of regulation, rather than in one direction.

 

 

https://www.ncbi.nlm...pubmed/28235489

 

 

https://www.ncbi.nlm...les/PMC5256118/

 

 

One of the steps in apoptosis is said to be the fragmentation of mitochondria. Apigenin fissions (fragments) mitochondria, as does resveratrol (in contrast to your link, which indicates the opposite). Still, you raise an interesting point as both cucurmin and butyrate are both said to cause mito fusion and yet result in apoptosis. So it seems likely that this protocol could oriented to either cancer or senescent cells merely by biasing to either fusion (with stearic acid instead of apigenin) or fission (with apigenin). Fusion is known to be bad for cancer cells, but fission is said to be bad for senescent cells, though fission per se is not going to kill them. 

[motorcitykid]

Turnbuckle,

 

What's you're opinion of the stem cell self-renewal protocol being a possible adjunct protocol to enhance the efficacy of IV stem cell treatment (placenta/mesenchymal cells)?

 

I surmise that, particularly in an older person (60's -80's), stem cells from the IV infusion would more easily assimilate if the senescent cells were to be destroyed and stem cell pool replenished through the stem cell self -renewal protocol prior to receiving the IV stem cell infusion.

 

There's no source of reference for this, I'm just popping off thoughts, assuming that the stem cells from the IV infusion might better assimilate because of an overall cleaner and healthier cellular foundation which might lend to a smoother, cellular migration and integration of those IV derived stem cells.

[Turnbuckle]

Turnbuckle,

 

What's you're opinion of the stem cell self-renewal protocol being a possible adjunct protocol to enhance the efficacy of IV stem cell treatment (placenta/mesenchymal cells)?

 

I surmise that, particularly in an older person (60's -80's), stem cells from the IV infusion would more easily assimilate if the senescent cells were to be destroyed and stem cell pool replenished through the stem cell self -renewal protocol prior to receiving the IV stem cell infusion.

 

There's no source of reference for this, I'm just popping off thoughts, assuming that the stem cells from the IV infusion might better assimilate because of an overall cleaner and healthier cellular foundation which might lend to a smoother, cellular migration and integration of those IV derived stem cells.

 

Unless you have zero stem cells left, why would you need an injection of exogenous stem cells when you can multiply your endogenous pools?

[motorcitykid]

Unless you have zero stem cells left, why would you need an injection of exogenous stem cells when you can multiply your endogenous pools?

 

https://www.ncbi.nlm...pubmed/24005862

 

From the paper:

 

"Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs (the term UCB-MSC refers to Umbilical Cord derived stem cells) had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence".    .

 

 "Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.

Edited by motorcitykid, 17 January 2019 - 10:24 PM.

[Turnbuckle]

https://www.ncbi.nlm...pubmed/24005862

 

From the paper:

 

"Although MSCs from different tissues have similar levels of surface antigen expression, immunosuppressive activity, and differentiation ability, UCB-MSCs (the term UCB-MSC refers to Umbilical Cord derived stem cells) had the highest rate of cell proliferation and clonality, and significantly lower expression of p53, p21, and p16, well known markers of senescence".    .

 

 "Our results demonstrate that primitive UCB-MSCs have biological advantages in comparison to adult sources, making UCB-MSCs a useful model for clinical applications of cell therapy.

 

 

It is very likely that pluripotent stem cells exist in adults--very small embryonic-like stem cells (VSELs)--that have been missed by a combination of their small size and the money already invested in exogenous treatments. 

 

A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells

Edited by Turnbuckle, 17 January 2019 - 10:57 PM.

[motorcitykid]

It is very likely that pluripotent stem cells exist in adults--very small embryonic-like stem cells (VSELs)--that have been missed by a combination of their small size and the money already invested in exogenous treatments. 

 

A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells

 

This is an interesting paper on VSEL's

https://www.ncbi.nlm...les/PMC6013546/

 

It seems that there are some unknowns about how VSEL's function in vivo. Do VSEL populations diminish with age?  If we assume that they do, and can be renewed via stem cell self renewal protocol, I still wonder:

 

From the paper:

 

"In addition, the main problem with the use of VSELs in regenerative medicine is their quiescence and limited number [17]. The ability of VSELs to expand in vitro is very limited, and requires a better understanding of their biology in order to stimulate their proliferative capacity without affecting their pluripotency"

 

But this is pretty darn exciting:

 

"When VSELs are induced to differentiate in co-cultures with a C2C12 supportive cell-line, a unique pattern in imprinted gene methylation is reverted that may explain in part VSELs quiescent status"

 

That's pretty interesting wouldn't you say?

Edited by motorcitykid, 18 January 2019 - 12:40 AM.