2503 replies to this topic

[resveratrol_guy]

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).

 

Thanks for this, Turnbuckle. I notice that this is still shown as the latest version in your profile. Some questions, hopefully not already answered upthread:

 

1. How often can this be done? What interval is optimal? (I understand that you like to alternate it with your stem cell self-renewal protocol.)

 

2. What sort of creative prescription process is necessary to obtain azithromycin? I've found antibiotics difficult to obtain, even in otherwise dodgy countries. And what dose?

 

3. If we're to believe the mouse studies, then dasatinib plus quercetin is more effective than either alone. So why not add dasatinib? (I'm not sure whether or not I'm in favor of doing so, as the last thing I want to do is reduce competition to dormant tumor cells, even if that competition is senescent. On the other hand, senescence is also bad and can create its own tumor cells, eventually. A 2-year rat study showed a modest increase in tumor incidence with 100-plus-mg human-equivalent daily dose, but of course we're not going to repeat this daily for years, but then again we have many more years for the results of our errors to manifest as tumors. Unfortunately I lost the link.)

[lost69]

Thanks for this, Turnbuckle. I notice that this is still shown as the latest version in your profile. Some questions, hopefully not already answered upthread:

 

1. How often can this be done? What interval is optimal? (I understand that you like to alternate it with your stem cell self-renewal protocol.)

 

2. What sort of creative prescription process is necessary to obtain azithromycin? I've found antibiotics difficult to obtain, even in otherwise dodgy countries. And what dose?

 

3. If we're to believe the mouse studies, then dasatinib plus quercetin is more effective than either alone. So why not add dasatinib? (I'm not sure whether or not I'm in favor of doing so, as the last thing I want to do is reduce competition to dormant tumor cells, even if that competition is senescent. On the other hand, senescence is also bad and can create its own tumor cells, eventually. A 2-year rat study showed a modest increase in tumor incidence with 100-plus-mg human-equivalent daily dose, but of course we're not going to repeat this daily for years, but then again we have many more years for the results of our errors to manifest as tumors. Unfortunately I lost the link.)

 

and why not to add fisetin which is shown to be such a potent senolytic.sorry if this has been discussed already, i found fisetin to be much more potent than all others senolytics, azithromycin included

 

thank you

[Turnbuckle]

and why not to add fisetin which is shown to be such a potent senolytic.sorry if this has been discussed already, i found fisetin to be much more potent than all others senolytics, azithromycin included

 

thank you

 

I'm only reporting what works for me. If fisetin works for you, by all means use it. 

[Kentavr]

and why not to add fisetin which is shown to be such a potent senolytic.sorry if this has been discussed already, i found fisetin to be much more potent than all others senolytics, azithromycin included

thank you

I apologize, however, Taxifolin is the strongest polyphenol. He has 5 OH groups. Fisetin has only 3 OH groups.

It is also the most bioavailable, since it is the most water-soluble (because the number of OH groups is greater).

It is also the least toxic (since it is more soluble in water than Fisetin and leaves the body faster)

The purest Taxifolin (99.5%) is produced by Ametis (Russia).

P. S .:
I know this topic very well, and I know what misconceptions are about Russia.

1. We have the most purified short peptides in the world (those of natural origin)

2. The cleanest and cheapest polyphenol in the world (Taxifolin)

3. The inventor of one of the world's most promising anti-aging compounds - SkQ1 - Skulachev (biochemist at Moscow State University). SkQ1 stops about 30 signs of aging in a mouse model.

[Turnbuckle]

Thanks for this, Turnbuckle. I notice that this is still shown as the latest version in your profile. Some questions, hopefully not already answered upthread:

 

1. How often can this be done? What interval is optimal? (I understand that you like to alternate it with your stem cell self-renewal protocol.)

 

2. What sort of creative prescription process is necessary to obtain azithromycin? I've found antibiotics difficult to obtain, even in otherwise dodgy countries. And what dose?

 

3. If we're to believe the mouse studies, then dasatinib plus quercetin is more effective than either alone. So why not add dasatinib? (I'm not sure whether or not I'm in favor of doing so, as the last thing I want to do is reduce competition to dormant tumor cells, even if that competition is senescent. On the other hand, senescence is also bad and can create its own tumor cells, eventually. A 2-year rat study showed a modest increase in tumor incidence with 100-plus-mg human-equivalent daily dose, but of course we're not going to repeat this daily for years, but then again we have many more years for the results of our errors to manifest as tumors. Unfortunately I lost the link.)

 

The senolytic protocol you quoted is not actually the latest, which I apparently neglected to post. I'm now using 2g each of nicotinamide and ribose one hour before to provide the necessary fission, while eliminating the apigenin. And sodium butyrate every half hour is very effective.

 

I go by the subjective feel of flu like symptoms for the senolytic part. It's natural that you would experience such symptoms since the flu propagates by stimulating apoptosis, which releases viral particles. My feeling is that three days in a row should be max, and I seldom do more than two. There's probably an age where cells aging out will reach a maximum, and before that you may not get much out of the senolytic part. For the SC part, I only do it once a week or two. 

 

As for azithromycin, I bought that from India a while back and it did almost nothing for me. The combination I posted seems safe, effective, and cheap, and those are always desirable virtues. I'm not a fan of exotic and expensive ingredients.

[resveratrol_guy]

The senolytic protocol you quoted is not actually the latest, which I apparently neglected to post. I'm now using 2g each of nicotinamide and ribose one hour before to provide the necessary fission, while eliminating the apigenin. And sodium butyrate every half hour is very effective.

 

In that case, would you mind making a new list of substances, quantities, and brands? It's quite handy to have each one of your protocols in one succint post, linked from your profile. But if you're tired of repeating yourself, then perhaps they should all be updated within your profile itself. You could then link back to it when you want to make a comment about your latest tweaks.

 

Also, are you aware of the Horvath study that reversed 4 different aging clocks? They used only HGH, DHEA, and metformin, which is remarkable, as they're in the "way old news" category insofar as most longevity enthusiasts are concerned.

 

https://www.nature.c...586-019-02638-w
 

Edited by resveratrol_guy, 07 September 2019 - 12:20 AM.

[Turnbuckle]

 

 

Also, are you aware of the Horvath study that reversed 4 different aging clocks? They used only HGH, DHEA, and metformin, which is remarkable, as they're in the "way old news" category insofar as most longevity enthusiasts are concerned.

 

https://www.nature.c...586-019-02638-w
 

 

 

They reversed it by 2.5 years. I reversed it by 11.2 years.

[resveratrol_guy]

They reversed it by 2.5 years. I reversed it by 11.2 years.

 

 

Yes, I read that! I wonder if their approach would be in some way additive to yours. Granted, it might incur other risks as well.

 

Of course I think the only thing that can be said of DNA methylation clocks is that they're a good measure of biological age vs. population norms in the absence of technological intervention, and therefore probably constitute suitable yardsticks by which to compare the relative merits of various senolytic therapies. What they indicate after such intervention is unclear, however, in particular because a few factors of the clock might progress more slowly, while others march on unaffected.

 

Too bad Osiris Green is no longer offering epigenetic testing. Perhaps mydnage.com is a viable alternative.

 

Also: I notice that sodium butyrate is sometimes available in mixture with potassium butyrate. This seems like a safer option, no? And if anything, I would replace the resveratrol with pterostilbene on account of the order-of-magnitude improvement in plasma halflife. For that matter, I don't think either one, in a few 100 mg doses, would do much of anything, even though there is indeed evidence that they're epigenetically therapeutic.

 

One other thing: How often do you do the protocol? I would image that we need to increase the frequency with increasing age. (It also wouldn't hurt to freeze some stem cells first, so you can always fill in the holes left in the cellular matrix after the fact, regardless of the state of your bone marrow or adipose reservoirs.)

 

Edited by resveratrol_guy, 07 September 2019 - 05:36 AM.

[QuestforLife]

Also, are you aware of the Horvath study that reversed 4 different aging clocks? They used only HGH, DHEA, and metformin, which is remarkable, as they're in the "way old news" category insofar as most longevity enthusiasts are concerned.

https://www.nature.c...586-019-02638-w

Growth hormone may be mobilising those hidden reserves of (very small) embryonic (like) stem cells that exist in our tissues.

https://www.ahajourn...SAHA.118.314287

Quiescent State of VSELs
VSELs residing in adult tissues are highly quiescent because of the erasure of regulatory sequences for certain paternally imprinted genes (eg, at the Igf2-H19 locus) and thereby protected from insulin/insulin-like growth factor stimulation.

Of course mobilising them in this way will likely exhaust them sooner

...the exposure of animals to increased insulin/insulin-like growth factor signaling leads to premature aging and depletion of VSELs from the tissues

So a protocol to increase their number (like Turnbuckle's) is preferable to simply stimulating their asymmetric division to tissues.

[lost69]

turnbuckle

 

i keep getting better and better (especially eyesight) by 3 days stemcells and 2 days apoptosis/senolytic protocol (everything back to baseline HRV values removing gdf11) but i m having bad/short sleep probably due to melatonin adenosine removal, can i take 4mg of this type of melatonin during these protocols or it may interfere?

 

thank you

Edited by lost69, 18 September 2019 - 11:20 AM.

[Vivian]

Am I certain that c60 effected a change in my thyroid levels?

No.

I am open to the simultaneous timing of ‘having taken c60 for 5 weeks’ and ‘the sudden unprecedented drop in my tsh’ as being coincidental. I have no proof, just immediately jumped to the conclusion that one caused the other.....

Lost69, I appreciate the question. Food for thought. Thanks!

Edited by Vivian, 25 September 2019 - 07:06 AM.

[QuestforLife]

After doing some reading around the subject, I’m fairy sure you’re wrong Turnbuckle that Threonine is vital to human ESCs (and we’ve all wasted money on buying this expensive supplement – but hey, that’s the life of a self-experimenter). The threonine requirement was shown unequivocally for mouse ESCs (https://www.ncbi.nlm...pubmed/19589965) and then tentatively extended to human ESCs (https://www.frontiersin.org/articles/10.3389/fcell.2014.00018/full ), although they never actually showed it beyond doubt. But since then there have been papers by other authors that have shown beyond doubt that human cells don’t need threonine, instead they use methionine (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(14)00122-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413114001223%3Fshowall%3Dtrue ) for the same purpose. This makes sense when you consider a couple of things: stem cells use methylation to remain pluripotent and quiescent; humans don’t have the threonine dehydrogenase enzyme so they can’t use it in the one carbon cycle in mitochondria to make methyl groups. It is not exactly clear why we can’t use glycine in the absence of methionine but it might be our limited supply is used for other things.

[Turnbuckle]

After doing some reading around the subject, I’m fairy sure you’re wrong Turnbuckle that Threonine is vital to human ESCs (and we’ve all wasted money on buying this expensive supplement – but hey, that’s the life of a self-experimenter). The threonine requirement was shown unequivocally for mouse ESCs (https://www.ncbi.nlm...pubmed/19589965) and then tentatively extended to human ESCs (https://www.frontiersin.org/articles/10.3389/fcell.2014.00018/full ), although they never actually showed it beyond doubt. But since then there have been papers by other authors that have shown beyond doubt that human cells don’t need threonine, instead they use methionine (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(14)00122-3?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413114001223%3Fshowall%3Dtrue ) for the same purpose. This makes sense when you consider a couple of things: stem cells use methylation to remain pluripotent and quiescent; humans don’t have the threonine dehydrogenase enzyme so they can’t use it in the one carbon cycle in mitochondria to make methyl groups. It is not exactly clear why we can’t use glycine in the absence of methionine but it might be our limited supply is used for other things.

 

 

The SC protocol presently comprises the following AAs--

 

Threonine — 5 g

Taurine — 5 g

Methionine — 3 g

Lysine — 2 g

Leucine — 5 g

https://www.longecit...-33#entry877893

 

 

Even while methionine is the main source of of human ESC nutrition compared to mice, it appears that threonine is still required in humans--

 

Threonine appears to be essential for proliferation of human as well as mouse embryonic stem cells

https://www.ncbi.nlm...les/PMC4206991/

 

[QuestforLife]

Even while methionine is the main source of of human ESC nutrition compared to mice, it appears that threonine is still required in humans--

Re your last reference (and my second one), they didn't actually show hESCs needed threonine, only that a (presumably competitive) analogue of threonine caused problems and that extra threonine (partly) rescued the situation.

But my final reference went one better and actually removed threonine from the hESC culture - and the cells were fine. Unlike when methionine (or to a lesser extent lysine or leucine) was removed. So my point still stands.

Edited by QuestforLife, 25 September 2019 - 03:13 PM.

[Turnbuckle]

Re your last reference (and my second one), they didn't actually show hESCs needed threonine, only that a (presumably competitive) analogue of threonine caused problems and that extra threonine (partly) rescued the situation.

But my final reference went one better and actually removed threonine from the hESC culture - and the cells were fine. Unlike when methionine (or to a lesser extent lysine or leucine) was removed. So my point still stands.

 

 

I'm not sure what you mean by they were fine, as the cell numbers were reduced from control for all of the AAs tested, but it does point to another AA that might usefully be added--

 

Deprivation of leucine (Leu), lysine (Lys), tryptophan (Trp), or Met resulted in inhibition of cell growth and decreased cell number (Figure 1A). 

https://www.cell.com...4131(14)00122-3

 

 

 

So it will certainly be worthwhile to change the AA mix to just those and see how it works.

 

 

 

Edited by Turnbuckle, 25 September 2019 - 03:55 PM.

[lost69]

I'm only reporting what works for me. If fisetin works for you, by all means use it. 

 

i have used your senolytic protocol twice adding 0.6g fisetin and 100mg gamma tocotrienols and the effect was very potent.i experienced herpes on lips but small and controlled with just an inflamed blister (no pus, no pain and so on) and an infected wound on leg, fatigue and light inflamation/pains like early during a flu.

 

wound was just a very small scratch while swimming, i think skin regrowth was very slow so it got infected in the pool and got nowhere by 7 days.then it needed to be cleared surgically from tissue not regrowing and i had to use oral antibiotic....infection resolved but it has a thick scab taking forever to heal (i think all process is now at 15 days for a 5mm scratch).i did not swim after it got infected

 

i have small leg wounds very often while swimming but i never got a thing like this getting infected in the water, resolving so slow and i never had to use oral antibiotics too (i don t even disinfect them) so this is definitely the effect of clearing senescence cells

 

early this year i had skin removed from a finger, a big piece 1.5cm large and i had skin regrowth by 24-48hrs, no scabs, no inflamation and could swim again by 48hrs.i think this was an effect of stemcells protocol (without senolytics) because i never experienced such fast healing and i guess unusually fast for a 50yo

[Kentavr]

i have used your senolytic protocol twice adding 0.6g fisetin and 100mg gamma tocotrienols and the effect was very potent.i experienced herpes on lips but small and controlled with just an inflamed blister (no pus, no pain and so on) and an infected wound on leg, fatigue and light inflamation/pains like early during a flu.

wound was just a very small scratch while swimming, i think skin regrowth was very slow so it got infected in the pool and got nowhere by 7 days.then it needed to be cleared surgically from tissue not regrowing and i had to use oral antibiotic....infection resolved but it has a thick scab taking forever to heal (i think all process is now at 15 days for a 5mm scratch).i did not swim after it got infected

i have small leg wounds very often while swimming but i never got a thing like this getting infected in the water, resolving so slow and i never had to use oral antibiotics too (i don t even disinfect them) so this is definitely the effect of clearing senescence cells

early this year i had skin removed from a finger, a big piece 1.5cm large and i had skin regrowth by 24-48hrs, no scabs, no inflamation and could swim again by 48hrs.i think this was an effect of stemcells protocol (without senolytics) because i never experienced such fast healing and i guess unusually fast for a 50yo

This is a good experience. Can you write all the drugs, dosages and time taken?

[ambivalent]

Lost, this sounds pretty extensive - my dosing has been intermittent - 2 x3 gram of fisetin dosing in the last week, along with liposomal quercetin and liposomal curcumin. Nothing for a few months prior. I assume you cannot separate out the benefits of the senolytics, but what have you observed on the upside?

 

Regarding my recent dose, the one thing I noticed was my weak knee briefly giving way the following day which it hadn't for a year or so (except when after previous doses of fisetin) which I assume to be senescent cell-clearance.

[Turnbuckle]

Lost, this sounds pretty extensive - my dosing has been intermittent - 2 x3 gram of fisetin dosing in the last week, along with liposomal quercetin and liposomal curcumin. Nothing for a few months prior. I assume you cannot separate out the benefits of the senolytics, but what have you observed on the upside?

 

Regarding my recent dose, the one thing I noticed was my weak knee briefly giving way the following day which it hadn't for a year or so (except when after previous doses of fisetin) which I assume to be senescent cell-clearance.

 

 

Be careful with senolytics as they can make you more subject to injury, and I'd advise against using any senolytic-type antibiotics or anticancer drugs with them. If you want to end their effects, take a stearic acid brownie, which should override mito fission and shut down apoptosis.

[QuestforLife]

Lost, this sounds pretty extensive - my dosing has been intermittent - 2 x3 gram of fisetin dosing in the last week, along with liposomal quercetin and liposomal curcumin. Nothing for a few months prior. I assume you cannot separate out the benefits of the senolytics, but what have you observed on the upside?

Regarding my recent dose, the one thing I noticed was my weak knee briefly giving way the following day which it hadn't for a year or so (except when after previous doses of fisetin) which I assume to be senescent cell-clearance.

Thanks for this report. I experienced something similar with my own senolytic experience - Azithromycin + Doxycycline + liposomal vitamin C for 2 days and on the 3rd day I replaced the Vit C with Nicotinamide.

On the first 2 days of the protocol all I noticed was a runny nose (and stomach upset from all the Vit C). Then a few days later I noticed my knees felt fragile and both wanted to give way for a few days. At the time I attributed it to other things.

[ambivalent]

@Quest this has been a consistent effect over the last year on the handful of occasions I've taken large doses of fisetin - initially there was a weakening then a strengthening (relative to pre-administration) of the knee. This is somewhat to be expected:

 

 

https://www.genengne...-new-cartilage/

 

@ TB yes, I've taken stearic acid through hot-chocolate after both doses. I added one drop to the first then two-three drops to the second dose - to a glass of the mix - of DSMO, which I hadn't previously, which I reasoned to be within safe parameters. 

 

I have felt somewhat sharper too, memory seems better, this is quite typical of fisetin. I ached for a couple of days, felt a couple of muscles niggle, but no flu-like symptoms when during the last dosing period a few months ago, I endured a modest cold for a week.  

[lost69]

have you discussed this study already?i dont know if relevant because they use "may be" too much...is urine levels of p16⁺EVs available commercially?

 

https://www.ahajourn...JAHA.119.012584

Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles Conclusions

Levels of p16⁺EVs are elevated in urine of hypertensive patients and may reflect increased proximal tubular cellular senescence. In EH, EVs originate also from distal tubules and in renovascular hypertension from Henle's loop. Hence, urinary EVs levels may be useful to identify intrarenal sites of cellular senescence.

[ryukenden]

They reversed it by 2.5 years. I reversed it by 11.2 years.

Was it according to the tests you did in 2018? Have you repeated since then?

[Turnbuckle]

Was it according to the tests you did in 2018? Have you repeated since then?

 

 

I reported most recently here. As the test has gone up to $300, I've won't get any more of them until someone comes along with a cheaper one.

[Graviton]

Does taking sublingual Epitalon go well with the stem cell protocol? Epitalon is a telomerase activator that can surpass the Hayflick limit in vitro, and there are some in vivo studies showing increasing the length of telomeres.

There have been discussions here before regarding whether taking telomerase activator increases epigenetic age or not, and we don't know its effects. In addition, it is not certain whether this significantly leads to effects of cell proliferation ability.

Certainly, cells have a certain limit of divisions and replications, and we have questions if this limit can be improved by telomerase activator in this protocol.

[Turnbuckle]

Does taking sublingual Epitalon go well with the stem cell protocol? Epitalon is a telomerase activator that can surpass the Hayflick limit in vitro, and there are some in vivo studies showing increasing the length of telomeres.

 

 

 

No. Do not use telomerase activators unless you want to become epigenetically older. It might be possible to use them once or twice a year, but regular use will ruin this protocol.

[resveratrol_guy]

Turnbuckle, what about the following:

 

1, Replace 50 mg resveratrol with 100 mg pterostilbene for longer plasma halflife.

 

2. Add 5g moringa oleifera for enhanced apoptosis (e.g. https://www.ncbi.nlm...cles/PMC4533244 ) Beware of potential nausea. Severely unappetizing!

 

3. Dissolve all ingredients (at time 0, at time 4h, and for all half-hourly doses of sodium/potassium butyrate) in a low-carb coconut milk base such as Silk Unsweet Coconut. Shake like hell to ensure all powers dissolve. The idea is to facilitate a steadier and more predictable release of all active ingredients, while avoiding stomach upset. (I prefer this to chocolate milk, as I think it's important to drive metabolically borderline cells, which are likely senescent, as deep as possible into energy crisis, so that they might more easily be killed by the other components of the protocol.)

 

4. Use sodium/potassium butyrate (e.g. Bodybio) instead of straight sodium butyrate for the sake of a healthier ion channel balance. (Queue all the related cancer risk discussion in other threads.)

 

5. (Add your one-hour prep window, beginning with 2g nicotinamide (niacinamide) and 2g D-ribose.)

 

6. Ideally, a 500 mg dose of berberine, to exacerbate the sugar crisis. Granted, this could be a problem in those who already have low blood sugar, or in those who are hepatically overwhelmed by the harsh substances already in the protocol.

 

Ironically, the protocol might work better for people like me, who follow high-carb diets, because it's a ketogenic shock to the system, above and beyond an apoptotic shock. (I plan to stay as close to carbless as possible for next day or three in order to prolong these shocks within reasonable limits.)

 

So far, I've noticed nothing apart from moderate nausea, which is surely due to the moringa. I'm also fighting some sniffles and chills, but that started in the prep window, prior to the first dose of senolytics, so it would seem to be a legit illness. At least, no brain fog thus far.

 

 

Edited by resveratrol_guy, 11 October 2019 - 03:52 PM.

[lost69]

turnbuckle

 

i did not study stemcell so i dont know if the fact of GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2⁺/CD133⁺ cells, can be useful to us on this protocol or even bad

 

https://www.ncbi.nlm...pubmed/31292540

TERT assists GDF11 to rejuvenate senescent VEGFR2⁺/CD133⁺ cells in elderly patients with myocardial infarction

Abstract

Growth differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in rejuvenating old stem cells after acute injury in the elderly population. This study aimed to evaluate the effects of telomerase reverse transcriptase (TERT) on GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2⁺/CD133⁺ cells, in elderly patients with acute myocardial infarction (AMI). We compared the quantity and capabilities of VEGFR2⁺/CD133⁺ cells from old (>60 years), middle-aged (45-60 years), and young (<45 years) AMI patients. The decline in circulating count and survival of VEGFR2⁺/CD133⁺ cells with age was accompanied by decrease in their TERT and GDF11 expression levels in patients with AMI. Further, upregulation of TERT could trigger GDF11-mediated rejuvenation of old VEGFR2⁺/CD133⁺ cells by renewing their survival and angiogenic abilities through activation of canonical (Smad2/3) and noncanonical (eNOS) signaling pathways. Depletion of GDF11 or TERT caused senescence of young VEGFR2⁺/CD133⁺ cells leading to impaired vascular function and angiogenesis in vitro and in vivo, whereas adTERT and rhGDF11 rescued this senescence. TERT cooperates with GDF11 to enhance regenerative capabilities of old VEGFR2⁺/CD133⁺ cells. When combined with TERT, GDF11 may represent a potential therapeutic target for the treatment of elderly patients with MI.

 

 

[Turnbuckle]

 

turnbuckle

 

i did not study stemcell so i dont know if the fact of GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2⁺/CD133⁺ cells, can be useful to us on this protocol or even bad

 

https://www.ncbi.nlm...pubmed/31292540

TERT assists GDF11 to rejuvenate senescent VEGFR2⁺/CD133⁺ cells in elderly patients with myocardial infarction

Abstract

Growth differentiation factor 11 (GDF11) is a transforming growth factor β superfamily member with a controversial role in rejuvenating old stem cells after acute injury in the elderly population. This study aimed to evaluate the effects of telomerase reverse transcriptase (TERT) on GDF11-mediated rejuvenation of senescent late-outgrowth endothelial progenitor cells (EPCs), defined as VEGFR2⁺/CD133⁺ cells, in elderly patients with acute myocardial infarction (AMI). We compared the quantity and capabilities of VEGFR2⁺/CD133⁺ cells from old (>60 years), middle-aged (45-60 years), and young (<45 years) AMI patients. The decline in circulating count and survival of VEGFR2⁺/CD133⁺ cells with age was accompanied by decrease in their TERT and GDF11 expression levels in patients with AMI. Further, upregulation of TERT could trigger GDF11-mediated rejuvenation of old VEGFR2⁺/CD133⁺ cells by renewing their survival and angiogenic abilities through activation of canonical (Smad2/3) and noncanonical (eNOS) signaling pathways. Depletion of GDF11 or TERT caused senescence of young VEGFR2⁺/CD133⁺ cells leading to impaired vascular function and angiogenesis in vitro and in vivo, whereas adTERT and rhGDF11 rescued this senescence. TERT cooperates with GDF11 to enhance regenerative capabilities of old VEGFR2⁺/CD133⁺ cells. When combined with TERT, GDF11 may represent a potential therapeutic target for the treatment of elderly patients with MI.

 

 

I imagine TERT+GDF11 would give short term benefits to such patients, but in this protocol I'm looking to reverse epigenetic aging. Insofar as TERT lengthens the telomeres of somatic and transit cells, allowing them to divide more times before senescence, it will do the opposite.

[Empiricus]

I threw away all the c60oo I had in the freezer.  I had added way too much hydroxytyrosol, and experienced no long-term benefits (albeit spurts of rejuvenation).  Wary of c60oo, I have stayed on the sidelines of this protocol, checking back now and again to see how its coming along. 

 

Now I'm looking at giving the protocol a go. Part of my thinking is it could help to compensate for damage caused by c60oo (replenish stem cells).  Moreover, the additional exposure to c60 in the protocol looks small compared to what I consumed in the past.  Also, as I have done a round of high-dose fisetin, and can see doing more rounds of it, ignoring the stem cell situation might not be smart. 

 

Is it safe to use the ses c60 that I bought 4 or 5 years ago?  It's been stored in a box in a closet in an air-conditioned room.  If I should toss the old stuff, what is the best option today for obtaining c60 material of the highest quality?  

 

As I am sensitive to polyphenols in olive oil, what would be the best oil to substitute?  (If  substituting olive oil will negate the benefits, then at least it won't be adding the extra HT which is what had caused me the most trouble in the past). 

Edited by Empiricus, 10 November 2019 - 08:04 AM.