1177 replies to this topic

[QuestforLife]

I believe you are right, quest, I misread and caught a summary from AI which suggested adding fisetin protected against DQ telomere-shortening but it looks the opposite, just the DQF result wasn't statistically significant as was the case in DQ. I will have a more thorough read to check when time permits - apologies.

 

No problem at all. The paper is confusingly written. Take a look just at the abstract:

 

 ABSTRACT Senolytics, small molecules targeting cellular senescence, have emerged as potential therapeutics to enhance health span. However, their impact on epigenetic age remains unstudied. This study aimed to assess the effects of Dasatinib and Quercetin (DQ) senolytic treatment on DNA methylation (DNAm), epigenetic age, and immune cell subsets. In a Phase I pilot study, 19 participants received DQ for 6 months, with DNAm measured at baseline, 3 months, and 6 months. Significant increases in epigenetic age acceleration were observed in firstgeneration epigenetic clocks and mitotic clocks at 3 and 6 months, along with a notable decrease in telomere length. However, no significant differences were observed in second and third-generation clocks. Building upon these findings, a subsequent investigation evaluated the combination of DQ with Fisetin (DQF), a well-known antioxidant and antiaging senolytic molecule. After one year, 19 participants (including 10 from the initial study) received DQF for 6 months, with DNAm assessed at baseline and 6 months. Remarkably, the addition of Fisetin to the treatment resulted in non-significant increases in epigenetic age acceleration, suggesting a potential mitigating effect of Fisetin on the impact of DQ on epigenetic aging. Furthermore, our analyses unveiled notable differences in immune cell proportions between the DQ and DQF treatment groups, providing a biological basis for the divergent patterns observed in the evolution of epigenetic clocks. These findings warrant further research to validate and comprehensively understand the implications of these combined interventions.

 

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[ambivalent]

Yes that certainly is confusing - I will have a more thorough at some point, as there aren't too many human studies with fisetin, though the number appears to be increasing. 

 

A couple of years back there was a study put out from the ITP suggesting there was no senloytic activity of fisetin found in the mice they tested (and no lifespan gain) - a little lazily I felt, Stansfield announced he would stop taking F+Q.

 

As far as I know there have been no in vivo human studies indicating fisetin reduces senescent cells but perhaps this provides some evidence, albeit weak, of senescent cell clearance expression through implied increased in telomere attrition (though not statsitically signfiicant). Or do you think there could be another explanation?

 

As an aside I was disappointed they didn't test DQF for CRP levels as for DQ where there appeared little difference. These protocols were different to those of another study, anyhow, where fisetin was studied on osteoarthritis where C-Reactive protein levels spiked dramatically months after the second course of fistein before returning to prior norms (day 45) 6 months later (8.9 - 32.5 - 9.2). 

 

https://clinicaltria...=17&tab=results

 

 

Anyhow, this is off topic, so I'll leave the fisetin chat there. 

  

 

 

 

  

[AngeloHealth]

Telomere extension via non-TERT pathways is still under-explored. The G-quadruplex stabilization angle (RHPS4 type compounds) actually offers a different lever than telomerase activators — preserving telomere length without driving proliferation. Worth pairing with mitochondrial-targeted antioxidants for the broader replicative stress picture; SOD enzyme upregulation in proliferating cells correlates well with telomeric chromatin stability in some cohorts. Anyone here have hands-on data with the more recent Astragalus extract standardization protocols?

[bullGenteel]

Thought I would share my experiments with pycogenol and nicotine. I am glad it got introduced to me here. I look forward to what your research says. I really respect the work done in this blog. I hope my experimenting might be a little helpful here. I think it is a lot to tackle such a monumental research topic such as telomeres. You work on high level theories; but I'm sure you aren't averse to doing some practical anti aging routines in the meantime. Even researchers usually run clinics with test subjects, I imagine, but I don't know much about science.

I am impartial because I have serious OCD, so I probably want to make nicotine work in your metabolic protocol whether or not is practical or even the best add on for it. I would wish to take it by itself for myself for now.

I trust your work here and research, I have gotten a lot of benefits. Even if I can't add much in way of the science. I can be impatient, so I have only experimented for about a week and a half. I was feeling like giving up when I hit a road block with sleep disturbances and too high of heart rate and I assume blood pressure. I do feel like I might be close enough to a viable method to use nicotine. I'm not sure about it working in your metabolic protocol; but I'd trust you as expert for that. I am impartial to just making nicotine work, perhaps just for some relief for a while till I feel more fully recovered from my brain injury, here's hoping.

I have had some success keeping my heart rate low and sleeping certain days thru experimentation. I think I may have figured out what works and why in a general not so deep scientificy basis. I found that if I took the leucine, niacin, pycogenol and nicotine, with the arginine my pulse could still go up 10 points or so; while It went up like 20 or more before pycogenol. My heart rate stays low if I follow a meticulous routine because I had to refresh my memory, and I have a bad memory. I reread it and there is a sensor for mtor that somehow relies on arginine and lecucine. So if you take Even a small dose of both together it activates mtor, with mtor by itself can raise blood pressure, right? If intermittent fasting can work with your protocol not withstanding sirt4 needs a well feed state; considering I need to not eat for like 6-8 hours in the morning for nicotine to work. As you mentioned in another thread the nicotine could spike blood glucose if taken with food.

For it to work I take the leucine, b6, pycogenol and .125 -- .25mg nicotine. The half life of leucine is like 1.5 hr, so I wait 2 hours or so than take arginine. Than I'd have to wait 2 hours is best to take the second dose of the metabolic protocol. Than wait another 2 hours, take arginine and wait 2 hours to eat; Since protein has leucine in it. I don't have the best working memory. If people are motivated enough to try nicotine with least amount of side effects. I take the arginine again at night about 1g roughly to not activate mtor. I take potassium and potassium ascorbate on an empty stomach though out the day. I also take egcg for gut health because I take a lot of taurine 3 days a week on off days from this protocol. I have to take pycogenol on the second day to keep my pulse lower (Haven't monitored my blood pressure). I wish I had researched pycognol a bit. I want to buy the cheaper pine bark extract to take on days inbetween taking nicotone to hopefully get the same function of lowering blood pressure/pulse without the cost. Perhaps just a higher dose of pycogenol could work in place of arginine, but I am trying to save money. I also took some black garlic and fish oil. I could see this protocol replacing a lot of suppleemnts, so the cost might factor in anyways.

I did find that the positive effects seem to be more energy similar to mitochondria boosting protocols. I was surprised to find that my test score in my brain training apps jumped like 10%, comparable to the boost I normally get from ginkgo. That made me think that ginkgo presumed to increase cereberal blood flow. So perhaps the pycogenol on its own gives same benefit, but nicotine is also known as a notrophic, I haven't tried pycogenol on its own. I never noticed a big boost from nicotine on its own. I also find my cognitive and energy benefits stay for the iterim between dosing every 3 days. I think the cognitive benefits and energy are dampened by high blood pressure atleast for me, if I don't correct for it adequately.

I also remember reading a blog post about James Watson. He believed getting oxidation deep into cells might be best way to prevent cancer. He lived into his 90's and played tennis into his late 80's. Perhaps pycogneol could have promote this as well, but I am sure you can research a lot into the real science, unlike me.

I see a possible connection with pycogenol and hypothrlyroidism, but perhaps its not too plausible. I know a close relation with hypothyroidism who never got a single Grey hair till in thier 70's. This relation seemed pretty youthful. I read that hypothyroidism might be pro longevity, obviously if treated, speculating because of a lower than average heart rate. Perhaps pycogenol could result in an artificial lower heart rate without the necessity of being an ultra athlete which would be pro aging by depleting stem cells and telomeres thru dividing more cells. I could see this could be an argument for pycogenol alone since the combo with nicotine may just keep heart rate spiking from the nicotine. Also vegetarians have lower heart rate and blood pressure, perhaps from lower mtor, which may be anti-aging. I am considering CR and vegetarianism. I stumbled on something by accident when trying to treat some IBS symptoms. I might share if I am not mucking up your thread too much. I was inspired by your posts about CR. I imagine a low heart rate would match the metabolic protocol nicely.

I have been taking the nicotine with the metabolic protocol every 3 days. I find the pulse rate died down on its own by the third day. To low of a nicotine dose, I didn't feel as much cognitive boost. I mentioned I think that nicotine receptors may be desensitized as well as can be upregulated anyways from nicotine use, so that guides my timing.

[bullGenteel]

Just a quick follow up to my last post. I thought about just taking arginine by itself. I know it is useful for fusion and has a similar half life to leucine. I tried it and I think it gives similar positive effects with quest's metabolic protocol that I got with the leucine. It maybe the sirtuli and amkp/fatty acid oxidation that is forwarded by quest that is only amplified by the nicotine and NNM and b6 I take. But I also googled a little to find that arginine is thought to promote those activities in the body. I'm not able to really able to absorb much scientific info on my own, so I rely on this thread that is very good at spelling things out for me.

I don't know if I would endorse nicotine for most people in this protocol. Likely you would get better benefits from whatever quest works out. I do enjoy the relief from OCD, though I have some personality disorderment to work at, and to continue to recover from a brain injury, and a underdeveloped hippocampus and hypothalmus, I suspect. I believe the progentor protocol may help to some degree with all three damages I have to my brain, but I'm still early in recovery and telomeres are also key to full restoration I believe from what I read here and my experiments with quest's protoocols.

My heart rate so far is around 60 upon waking. I am an endomorph and have had low blood pressure consistently, but I havent checked lately. My pulse does rise however up to arpund 74-76 by evening. It also seems to rise 10 pts after eating. I could maybe lower it with dosing more pycogenol. I don't know if that is ideal, I have never really kept track of my heart rate before. I am able to sleep for the most part, but I have to work out histamine and serotonin, I have always had trouble with sleep.

I am not in good shape presently, I am not working out really at all. In the past I measured my heart rate once a day and at times it was anywhere from 58 to 73, due to being in better shape back then. I am in my early forties and a low BMI, I am sure from constant experiments with fasting and recently fmd and CR sporadically incorporated with quest's progentor protocol. I jotted down like 4 pages of notes on those experiments, before taking nicotine for notrophics. I'd have to edit it, but I don't want to muck up someone's thread. It's 99% drawn from quest's posts I just experiment on some his valuable tangetial points made and make a couple observations of my own or tweaks. I have trouble with logic and working memory so I am not sure the quality of my experimenting.

I have always had mild angina like chest pains following a serious accidnet (Edit: a family member mentioned likely due to inflammation in intercoastal musceles, not really heart related, unless it Cytokines
can put stress on heart... I can be a hypochondriac and have no knowledge in medicine, but magnesium helps). Another user had similar pains and he said coq10 helped. I use to get these pains almost constantly, with a stress test that came back healthy. I found after a year or more of consistent antioxidant and anti inflammatory supplemental stack, the pains were lessened and very infrequent. I have also always found topical spray made from water an epsom salts gave instant relief. I just mention this because I use this spray often along side potassium ascorbate, potassium salt, arginine a few times a day and natural ace inhibitors, seems to make the nicotine use seem more practical, but I am not certain on its longterm use.

If I had high blood pressure or what not I would be really cautious. My pulse I measured at about 84, when I didn't add pycogenol. I might get mild angina like pains or mild tightness/tingling to use the epsom salts. I may try adding pine bark extract and another form of potassium. I looked into a potassium topical spray but the potassium ions apparently are larger than magnesium. Another forum user used 40 proof alcohol to dissolve the potassium for better absorption? It gives some added security, since potassium channels and electrolyte balance in the heart is thrown off due to nicotine.

Edited by bullGenteel, 05 June 2026 - 07:01 PM.

[QuestforLife]

I generally take the b6/leucine (with or without variants such as myricetin, low dose Cu/res, etc) at bed time. I do experience increased BP but not noticeable HR elevation. This is pleasant at night. I do not take Nicotine or niacin etc at this time as I don't want a stimulant at that time. I do sometimes take niacin earlier with my evening meal, particularly if it is carb heavy.

I find nicotine to be a pleasing stimulant but I don't take it very often. I would save it for when you are not eating. It is the opposite of niacin, keep it away from meals.

Edited by QuestforLife, 05 June 2026 - 06:40 PM.

[bullGenteel]

I usually just make some posts on this forum based off stuff I read, experimented on or have thought about a while. I don't really feel that equipped for back and forth exchanges for various reasons. I'm not the most outgoing right now. I imagine I score pretty low in working memory. I usually read pretty slow, but I had a test say I was so many years advanced in reading comprehension. I do struggle with logic and memory. I have an imbalanced IQ, so my best talent may be sticking at problems where a more balanced approach may say move along, nothing to see here; while I would get stuck at a problem and may end up seeing some novel or not so novel/useful ideas. Might be similar to adhd needing to adjust and function differently compensate for some limitations. I also am recovering from a brain injury. I imagine I'd still need some more rounds of your progentor protocol. I am pushing myself to see how much I can push myself to improve a bit in exectutive function. I have trouble with motivation and change, so I maybe should start a thread on that, but not right now.

I wouldn't start a thread really on anything I have tried here because as I stated I respect your research here and I just try out some tangents you cover in your high level scope of work. Unless I am mucking up the thread. For some of these reasons listed I probably struggle a lot to experiment on a day to day basis. I like to keep things more simple to manage. I am sure it would be advantageous to experiment and optimize things.

Fo NAD+, I have some extra NMN, I found discounted, hopefully it wasn't sitting in a back of a truck that I keep in the freezer. I should keep notes, I didn't know niacin should be taken with meals, I don't mind the flush. I guess I'd have to take it on weeks I don't take nicotine. I thought with the upregulation, I feel that atleast the ocd relief lasted for a couple weeks after use. I imagine I have to watch blood pressure while taking nicotine.


I might post some questions or I dont know, write an essay. I dont know if either will help me surmise some improvements I noticed from experimenting with CR and your progentor protocol. I imagine you could tell me if some benefits I noticed with some CR experimenting is fruitful or not. I found out by a happy accidnet, by trying to reduce some IBS symptoms. CR was on my radar because you posted about it and intially thought keto would work iwrh your protocol. I didn't glean much, since I need things simplified to comprehend not think for myself, ha ha. It also wasn't as great of effect as your progentor protocol but better than just fasting.

I forget what I was gonna ask about reverstarol, or likely I didn't know what to ask. It might have been about CR and reversatrol. I did just google that Pterostilbene at a lower dose could reduce blood pressure when combined with grape seed extract. GSE is what did me bad wirh senyiotics. A quick google search says pycogenol may share some polyphenols/flavanols, or what not, in common with GSE or chocolate. Maybe those could be experimented with in your surtulin/metabolic protocol if you havent tried yet? I believe low dose reversatrol may not affect BP advantagously enough. It said Pterostilbene could increase cholesterol, but can be mitigated with lower doses combined with GSE or mote rightly, hopefully pycogenol. (Edit: maybe low dose is the way to go every few hours. Thats all I ever done when using reversatrol. I used it a month or so a go so maybe I dhould use it again for 10 days, if thats what you advisee still?) You put out a warning about reversatrol can oxidize cholesterol, as I remember, without feeling versed myself truely on the medical or science side. I am sure I found low dose reversatrol resulted in significant improvements for me with your herbal progentor protocol than when I experimented without. I may have gotten even more improvements, had I used telomere agents sooner like you advised in your guide. I noticed more improvment perhaps such as fading of spider veins; just from low dose gotu kola use in a modified progentor protocol.

I'll see if my experimenting can be both a little useful to your research and hoping it will continue to help me to recover. Sorry if my responses aren't the most organized or concise.

Edited by bullGenteel, 07 June 2026 - 06:43 AM.

[bullGenteel]

I discontinued the nicotine for now till I order some more pine bark, potassium gluconate powder, and perhaps the pterostilbene. I do feel much calmer the last couple days just taking leucine, b6, and nmn. The nicotine has been out of my system 3 or 4 days. I will probably measure my blood pressure, I'd suspect my blood pressure was mildy elevated not just pulse. I still feel lingering, significant relief from OCD, as I expected. I probably have lessened notrophics effects.

I did notice brighter colors today. I am sensitive to seeing brighter colors with some neurogenerstive protocols. If I hadn't used the sauna in a while, combined with brain aggregate dissolving substances results in brighter colors and clearer thoughts due to my brain injury, or less bright and clear if I don't protect the removal there of.

I would chock my feeling better in support of your suggestion to change the line up of attack with metabolic enhancement. I feel subtly better presently, than other weeks when I just took one mode of metabolic stimulation compared to two. I imagine I could take nicotine interspersed with other various modes. Like by adding reversatrol, it could probably be healthy to enhance some pathways for metabolism thru sirt 1; while turning some pathways down and others up, as is probably naturally done by the body during repair and rebuilding phases.

Just reading a bit like reversatrol could turn off some anti-cancer mechanisms like p53 to allow repair, but you would want it on sometimes. I've got along ways to go to understand your research, if I ever hope too. I probably should have taken even more notes, at times when I read thru your thread. I have always read about receptors being desensitized but you go into a much more breath and depth than that.

So taking different approaches to the metabolic enhancement seems synergistic, safer, and more optimal.

I don't feel that capable of experimenting too much with my lack of working memory, I have an avoidance type personality disorderment, amoung others; as well I also don't like to touch on my sensitivity to insomnia.

I mentioned pterostilbene, I think you mentioned experiments with it a couple times in your blog and mentioned blueberries for telomeres. If this is why you said reversatrol can be both good and bad, but I suppose same may be true of all forms of it.

I had planned to try to start to write more concise posts. I planned to do that when I get around to share my short experience and some positve effects and little suggestions for calorie restriction if it could fit into any of your protocols or not. I'll try to edit down my notes to major points, if that will be less jumbled befote I post, if I can manage.