2523 replies to this topic

[Mind]

Chemically induced reprogramming to reverse cellular aging was published 2 days ago. It examines using small molecule cocktails to achieve the same results as complicated genetic interventions in reducing aging. There are 6 cocktails examined.

 

There are a lot of ideas in the paper. Some of the small molecules might be candidates for incorporating into this protocol. I see that alpha ketoglutarate is mentioned as increasing iPSC efficiency. Forskolin and valproic acid were mentioned as being "likely to work in the early stages of CiPSC formation", where work means "achieve age reduction without altering cell identity". 

 

In the discussion section, the authors had this to say about forskolin:
 

 

I don't think this post is that far off topic and therefore I will leave it here. People can use the link and go to the new discussion if they want to discuss cellular reprogramming as a stand alone topic.

 

Thanks to everyone for thinking about the flow of this discussion and suggesting ways to make it continue in a productive manner.

[FWP]

Third test date 2022-12-08
Biological age: 51.7
Chronological age: 58.8
Delta: 7.1

There were about 10 stem cell protocol rounds between the 2022-03-06 measurement The latest test was not the best of results. My delta decreased by 13.2 years. I'm not taking resveratrol.

You are mentioning 10 stem cell protocol rounds. May I ask how many days you are doing the senolytic/ fission part in one round?

Edited by FWP, 19 July 2023 - 03:37 PM.

[stephen_b]

You are mentioning 10 stem cell protocol rounds. May I ask how many days you are doing the senolytic/ fission part in one round?

 

1 day fusion, 2 days fission generally. I had been doing 1 and 1 originally when I saw the greatest gains, and so I was considering going back to that.

[FWP]

I was under the impression that turnbuckle did 1 day fusion and 2 days fission and that sometimes 2 times a week. Than Dr David Sinclair seems to have slowed down his own aging and looking at his stack of supplements he seems to be constantly in a fission state. My idea is it could be important to stay more in fission and this protocol is strong as it sometimes alternates to fusion generating new stem cells.

[Repack Racing]

I put the post in the cellular reprogramming thread here. I'll report my own post since I'm not sure how to take it down.

 

I thought it was relevant to see how elements of that paper's findings might be incorporated into this protocol. After all, the protocol has changed over time.

 

For example, could forskolin be helpful when taken on the fusion day?

stephen_b

 

This was good to post here.  I personally can't keep up with many threads and I am glad to have this study information.  There will always be members who can't help but comment about off-topic posts. Look at how much conversation this sparked!

[Kelvin]

Anyone have any ideas on ways to eliminate defective stem cells?

The body has existing pathways to destroy them. Is there a way we can artificially accelerate and enhance these mechanism on a larger scale, something like the mitochondrial protocol’s use of PQQ to expose methylated mitochondria for elimination?

Would a senolytic like fisetin or quercetin kill damaged stem cells like they kill senescent cells?

Edited by Kelvin, 04 August 2023 - 01:05 AM.

[MarcD]

Have a look at this:

https://pubmed.ncbi....h.gov/26657143/

[Kelvin]

Interesting.

But it is a pharmaceutical that would probably require a prescription.

Is there any supplement with a good safety profile that can also eliminate damaged stem cells?

[Kelvin]

Fisetin MIGHT be effective at reducing senescent stem cells in favor of more functional stem cells.

Perhaps taking the mito protocol with 100 to 300 mgs of fisetin added to the mito fission days before starting the C60 protocol would be effective, unless someone has a recent injury because fisetin might eliminate damaged cells that, despite being damaged, are needed to direct where stem cells are supposed to deploy during the healing process.

https://www.nmn.com/...senolytic-agent

Liu and colleagues found that fisetin treatment eliminated senescent cells in the muscle of progeria mice, as expected from a senolytic. They also found that fisetin reduced the number of fat stem cells, some of which could have been senescent. Furthermore, fisetin increased the number of muscle stem cells, suggesting that their proliferative capacity had been restored. Along with other experiments, these findings suggest that fisetin restores muscle stem cell function by eliminating senescent fat stem cells.

[Kelvin]

Fisetin also decreases telomere length.

So if you use fisetin before the C60 protocol it is probably better to increase the use of astragalus root from once every 10 C60 cycles to once every 7 to 8 C60 cycle to prevent good stem cells from prematurely going senescent because of fisetin use.

[Bike_to_120]

Been using this protocol weekly for 6 months now. Had my epigenetic age measured by Trudiagnostic. Went from 50 to 45 - chronological age is 70.

Seems to be working as this was the major protocol change since my last test.

[dlewis1453]

Been using this protocol weekly for 6 months now. Had my epigenetic age measured by Trudiagnostic. Went from 50 to 45 - chronological age is 70.

Seems to be working as this was the major protocol change since my last test.

 

That's a great result. Thanks for sharing! 

 

The delta between your epigenetic age and your chronological age is huge. What did you do to get your epiage down to 50? 

[Turnbuckle]

Been using this protocol weekly for 6 months now. Had my epigenetic age measured by Trudiagnostic. Went from 50 to 45 - chronological age is 70.

Seems to be working as this was the major protocol change since my last test.

 

Most impressive. And I note the post you made on March 5 --

 

Had 3 tests: bio age (chrono age)

 

epiagingusa 56(68)

Trudiagnostic (50 (69)

Trume 60 (70)

 

Tally 69(69)

 

 

So three tests from three companies, and while the results vary quite a bit, they all show your initial epigenetic age remarkably below your chronological age. (Though I don't understand what the "Tally 69(69)" means.)

 

So that begs the question, what was your previous protocol, assuming you had one?

 

Also, you mentioned in another post that you were taking low dose naltrexone. Had you previously noticed any overall health benefits from that? Any evident age reversal?

[Bike_to_120]

Most impressive. And I note the post you made on March 5 --

 

 

So three tests from three companies, and while the results vary quite a bit, they all show your initial epigenetic age remarkably below your chronological age. (Though I don't understand what the "Tally 69(69)" means.)

 

So that begs the question, what was your previous protocol, assuming you had one?

 

Also, you mentioned in another post that you were taking low dose naltrexone. Had you previously noticed any overall health benefits from that? Any evident age reversal?

 

My previous protocol that made biggest reduction in methylation age was rapamycin/metformin. There was a large drop 3.5 years ago when I started rapamycin.

LDN significantly dropped my cRP significantly from the 4's to 1.5 - not sure if it changed epi age although it does in the Levine calculation

Tally is Tally Health - David Sinclairs company. I participated in their initial research to determine their correlation so they assigned my age to their calulation

[Turnbuckle]

My previous protocol that made biggest reduction in methylation age was rapamycin/metformin. There was a large drop 3.5 years ago when I started rapamycin.

LDN significantly dropped my cRP significantly from the 4's to 1.5 - not sure if it changed epi age although it does in the Levine calculation

Tally is Tally Health - David Sinclairs company. I participated in their initial research to determine their correlation so they assigned my age to their calulation

 

Metformin appears to be a strong senolytic. My own recent experience with 500 mg (for blood sugar) was fatigue and strong flu like symptoms the first day, which declined on days 2-3, and disappeared thereafter, even with three times the dose. This for me is typical of senolytics. Once the senescent cells are disposed of, it can take a while for them to build up again. It may also be a good idea to alternate senolytics, as their effectiveness in different tissues will likely vary.

 

Note that some researchers (eg, this paper) worry that removing cells with senolytics can deplete stem cells that are called on for replacements. This objection is eliminated by the occasional use of C60 + fusion. 

[Kelvin]

Fisetin has been shown to give mice a small to modest increase in lifespan, usually around a 5% to 15% extension.

Part of the reason for this may be that it clears out defective stem cells thus freeing room in stem cell niches to be populated with healthier stem cells.

Since the niches cannot store more than 100% of their capacity for stem cells it is important that what stem cells exist are populated with the healthiest possible stem cells.

Using the mito protocol once or twice with 100 mgs of fisetin on the fission days before using the C60 protocol would help clean out any damaged stem cells before the pools are repopulated by the protocol.

Of course, fisetin should not be overused in an excessive way because it shortens telomeres and might push healthy cells into senescence and apoptosis prematurely.

One might also want to avoid a senolytic before the C60 protocol if your stem cell pools are low (because someone is using it for the first time) because a senolytic like Fisetin might wipe out the limited number of stem cells in close to empty niches.

Edited by Kelvin, 21 August 2023 - 10:12 PM.

[timedilation]

Metformin appears to be a strong senolytic. My own recent experience with 500 mg (for blood sugar) was fatigue and strong flu like symptoms the first day, which declined on days 2-3, and disappeared thereafter, even with three times the dose. This for me is typical of senolytics. 

 

Interesting observation.  That would fit with Metformin's suspected effects as a mitochondrial inhibitor, but on a quick search I can't find any studies on its senolytic activity.  Seems to me that this should have been a pretty obvious thing to test, especially given how long Metformin has been in the longevity space.

[Turnbuckle]

Interesting observation.  That would fit with Metformin's suspected effects as a mitochondrial inhibitor, but on a quick search I can't find any studies on its senolytic activity.  Seems to me that this should have been a pretty obvious thing to test, especially given how long Metformin has been in the longevity space.

 

Metformin has been called a "senostatic," though not a senolytic. However, the effect I observed was not with metformin alone, but in combination with supplements I was already taking to control blood sugar, like quercetin, berberine, ALA, and omega 3 oil, which even together were not that effective at lowering blood sugar to any great degree. I suppose I could cut them all out except metformin, and bring them back one at a time, though sorting out effects in a single individual would be difficult, due to the slow increase in senescent cells.

 

If there is an interaction, I'd put money on quercetin.

Edited by Turnbuckle, 22 August 2023 - 10:09 AM.

[QuestforLife]

 

Note that some researchers (eg, this paper) worry that removing cells with senolytics can deplete stem cells that are called on for replacements. This objection is eliminated by the occasional use of C60 + fusion. 

 

Michael Fossel is a telomerase advocate. His objection is not that stem cell numbers will be reduced by senolytics, which your protocol addresses (if it works by the mechanism you have described), but that telomeres (in stem cells) will be depleted.

 

This, as far as I am concerned, is not addressed by your protocol, and we know telomerase activators cause a large increase in epiAge when combined with your protocol, so it remains an open question.

 

In my own experiments I've experienced epiAge acceleration several times when combining telomerase activators with stem cell stimulants. The most recent occasion was using your protocol. But I found 3 months later that epAge had returned to its lower baseline, without me changing anything. So my working theory is that combining TAs with stem cell stimulants causes a spike in cell numbers due to increased divisions made possible by the telomerase (and hence epiAge acceleration), but that once the growth in cell numbers tails off, epiAge returns to normal. These are mainly blood cells we are measuring, so they are highly dynamic over month timescales. This is a highly plausible theory to me, but it is speculative. We don't really know what the telomerase activity of stem cells is in vivo, so it may be that Michael Fossel's concerns are not warranted. Or he may be technically correct, but in a practical sense the reduction in stem cell telomere lengths may not become a concern for a hundred years. We just don't know. I'd like to see a widely available and cheap telomere test to go alongside these epiAge tests, so that we can answer this question.

 

On a side note, it is very good to see you back on the Forum Turnbuckle. Long may it continue. 

[Turnbuckle]

Epigenetic age is far more malleable than most people believe, and can be driven in both directions. As I've previously reported, the injudicious use of telomerase promoters with my protocol rapidly increased my epigenetic age and reversed the progress I'd made. It took a year to get my gains back. This rapid aging was also physically apparent, as my wife and others said I was looking older. And even though telomerase may be lacking in many adult stem cells, do we really want to aid defective SCs when we have a method of proliferating SCs en masse? Without telomerase supplements, the SC niches will simply become enriched with SCs that make sufficient telomerase, while those without telomerase will be eliminated by the telomeric clock. A form of cellular eugenics. 

[QuestforLife]

Epigenetic age is far more malleable than most people believe, and can be driven in both directions. As I've previously reported, the injudicious use of telomerase promoters with my protocol rapidly increased my epigenetic age and reversed the progress I'd made. It took a year to get my gains back. This rapid aging was also physically apparent, as my wife and others said I was looking older. 

 

I took full daily biomarkers and the epiAge acceleration I experienced was not accompanied with a noticeable physical deterioration, though I accept different people may have a different response, and you are older than me so you may be a better model for people using this protocol. All I am saying is that in my case epiAge acceleration reversed itself in about 3 months, see here and here.

 

 And even though telomerase may be lacking in many adult stem cells, do we really want to aid defective SCs when we have a method of proliferating SCs en masse? Without telomerase supplements, the SC niches will simply become enriched with SCs that make sufficient telomerase, while those without telomerase will be eliminated by the telomeric clock. A form of cellular eugenics.

 

I like the idea of cellular eugenics, and I hope it is true, but this is speculative. Like I said, once I get my hands on a cheap telomere test, I will take it regularly alongside epiAge tests, and eventually we'll get to the bottom of this. 

[dlewis1453]

How are your longevity results lately Turnbuckle? Have you experienced continued improvement since the last time you were on here? It's good to see you back here. 

[lost69]

Epigenetic age is far more malleable than most people believe......

 

very glad to see you back on here, i am going to start 60 sessions of hyperbaric chamber next week for my humeral head osteonecrosis (which has been stable on stage 1 for 3 years with very little symptoms now) 

 

do you think this protocol might be mixed with hyperbaric chamber sessions to get better results for both antiaging and bone?

 

i have very old bottles of C60, at least 2 years old, seller says they are ok.do you think it is better to use new ones 

 

thank you

Edited by lost69, 05 September 2023 - 08:51 PM.

[joesixpack]

very glad to see you back on here, i am going to start 60 sessions of hyperbaric chamber next week for my humeral head osteonecrosis (which has been stable on stage 1 for 3 years with very little symptoms now) 

 

do you think this protocol might be mixed with hyperbaric chamber sessions to get better results for both antiaging and bone?

 

i have very old bottles of C60, at least 2 years old, seller says they are ok.do you think it is better to use new ones 

 

thank you

 

Regarding the old C60 EVO, if it was not exposed to light, and stored unopened in a cool dark place, it is probably ok. Try smelling and tasting it first.

 

New supplies are probably best if you are looking for results

[HBRU]

Sorry for this question.

But what is (or where is) the latest most accurate version of the protocol ? My sympathy and thankfullness to Turbuckle. Hope he comes back.

[njurkovi]

I would like to report my results after following the latest Turnbuckle protocol (feb-may around 10 rounds of the protocol) and

the latest Kelvin modification (july-august, around 7 rounds of the protocol):

 

Results of Trume tests

               bio age         chrono age

1/23         63                 61

5/23         58                 62

9/23         55                 62    

 

 

 

The protocols obviously had an effect of bio age, however unlike other reporters here, I can not say that the protocols made a big difference

in my appearance (skin, hair, scars etc) or general state of being. Maybe some age related 'aches' are gone, but I wouldn't put this above the placebo level.

 

This made me curious as to whether tests that are based on natural methylation can be extended to reliably predict the results of 'manipulated'

methylation.

 

I would appreciate if somebody with more knowledge of biology (and apparently statistics) would comment on Josh Mitteldorf's post bellow, as

well as the papers he is referencing:

 

https://joshmitteldo...-interventions/

 

 

[Mind]

I would like to report my results after following the latest Turnbuckle protocol (feb-may around 10 rounds of the protocol) and

the latest Kelvin modification (july-august, around 7 rounds of the protocol):

 

Results of Trume tests

               bio age         chrono age

1/23         63                 61

5/23         58                 62

9/23         55                 62    

 

 

 

The protocols obviously had an effect of bio age, however unlike other reporters here, I can not say that the protocols made a big difference

in my appearance (skin, hair, scars etc) or general state of being. Maybe some age related 'aches' are gone, but I wouldn't put this above the placebo level.

 

This made me curious as to whether tests that are based on natural methylation can be extended to reliably predict the results of 'manipulated'

methylation.

 

I would appreciate if somebody with more knowledge of biology (and apparently statistics) would comment on Josh Mitteldorf's post bellow, as

well as the papers he is referencing:

 

https://joshmitteldo...-interventions/

 

This is something I have noticed for a while now. We have a lot of objective evidence from biohackers now (thanks for sharing yours!). People are definitely reducing their biological age according to many metrics, however, hardly any of the biohackers I know or converse with are seeing their wrinkles go away or their grey hair becoming colored again. For men, they most certainly have not seen their hair grow back. Even Steve Perry (gdf11) looks older now than when he started his regimen 9 years ago.

[njurkovi]

I wonder if there is a negative reporting bias - I almost felt bad reporting 'no obvious result' when a majority of people report all these wonderful effects (at least in the majority of posts that I read).

I also want to say that I am very grateful to Turnbuckle for making his protocol available - it did exactly what it claimed -- lowered the bio. age.

But the discussion worth having is, to what extent does lowering this number increases longevity / quality of life.

[Bike_to_120]

This is something I have noticed for a while now. We have a lot of objective evidence from biohackers now (thanks for sharing yours!). People are definitely reducing their biological age according to many metrics, however, hardly any of the biohackers I know or converse with are seeing their wrinkles go away or their grey hair becoming colored again. For men, they most certainly have not seen their hair grow back. Even Steve Perry (gdf11) looks older now than when he started his regimen 9 years ago.

I did not report it previously but my chest hair has definitely changed. From my 50's into my 60's the hair became very long and very grey (3")

Now the hairs are shorter like they were in my 20's and definitely brown and not grey. A very noticeable change.

My beard is still grey and my head hair has never turned grey. No new hair.

[Kelvin]

I wonder if there is a negative reporting bias - I almost felt bad reporting 'no obvious result' when a majority of people report all these wonderful effects (at least in the majority of posts that I read).

I also want to say that I am very grateful to Turnbuckle for making his protocol available - it did exactly what it claimed -- lowered the bio. age.

But the discussion worth having is, to what extent does lowering this number increases longevity / quality of life.

How good was your health overall before you started the protocol?
 

If you were in decent shape already (62 isn’t that old) then there may not have been much room for improvement, sort of how younger users with already healthy mitochondria don’t notice much improvement from the mito protocol. 
 

A lack of change in grey hairs and older scars could be a result of the fact the protocol cannot restore already empty stem cell niches.