When I stay on schedule, I take a cocktail of fisetin, quercetin, theaflavin, apigenin, and some aids to assimilation every month or so for a 2-3 day run. If this sounds loose, it is because I have never fully committed to the practice or the underlying research. When I took the cocktail this time, it had been several months since doing so. Within eight hours, I experienced a profound sense of fatigue that took several days to dissipate.
The experience could have been coincidental; perhaps I was shaking off a minor virus. Has anyone else had this experience when attempting to reduce their population of senolytic cells hanging around?
I perform senolytic interventions much less frequently nowadays. When I first initiated senolytic therapy in spring 2019, I experienced a pronounced reduction in low‑grade (“cold”) inflammation. Over time I experimented with several protocols and compound combinations. The most effective regimen consisted of fisetin combined with piperlongumine, quercetin, and theaflavins.
As the magnitude of the response has diminished—possibly due to concurrent use of rapamycin or taurine—I now limit senolytic sessions to approximately three times per year.
I have done 2 cycles with FOX04-dri in202r. BUT previous to that had been doing 4 cycles of very high dose Q+F+supporting compounds 4 times a year since 2019
I did not notice much with regard to fatigue with either approach.
Thank you for your response. That’s a lot of cycles (!) I am considering just using FOXO4-DRI. I was thinking a cycle of SS-31, Epitalon, then hit FOXO4-DRI along with MOTS-C, and then three weeks using 10mg all trans retinoic acid (ATRA) along with an amino stack and some minerals that will support Loxl (so copper, manganese, etc) specifically for tropoelastin upregulation and incorporation. I’m currently trying to get ATRA from India, since there’s no way anyone in N. America will prescribe that for biohacking.
Have you jotted your protocols down somewhere for us to see? I am very interested.
And have you done any testing? idk if that’s even feasible… FOXO4-DRI is already costing ~$300 for 50mg, not to mention the other compounds.
I take 1.5g of quercetin on day 1, day 3, and day 5 of each month (4.5g total pulsed over a 5 day span). I take a highly absorbable form of quercetin along with some fat to additionally aid absorption.
I experience no fatigue or any other adverse symptoms.
FOX04-DRI is the only known senolytic that has the potential to kill more types of zombie cell than any other know senolytic. Yes there is more than 1 type of SNC, just as there is more than 1 cell type in our body.
The polyflavonoids are limited in the SNC type they can clear, endothelial and adipose cells that have become senescent is where they appear to have influence.
While FOX04-DRI is not “universal” it is very selective and covers more SNC types that the popular Q and F do.
wow, i took it for 2 weeks non stop, probably wrong way to take it as we are meant to do it only 2 or 3 days per month?
i recall having super vivid dreams at night
i felt i was outside my body observing myself when i was awake and at work
it made working impossible my brain was weirded out
i stopped it after 2-3 weeks haha
never got back to it
i also tried spermidine, no real effects except it seems to make my brain a bit different the next day if i take it before sleep? i can feel it slightly.
thanks @Steve_Combi I bookmarked them. What did you think of the cycle I posted?
I went ahead and ordered the ATRA. What a pita ordering from RL; wire transfers and all that bs. I sent him a followup email pleading that he opens a crypto account. Fingers crossed that the order gets here.
Not a lot of real benefit from that. The full elastin assembly process ends around the age of 13. Even if the raw materials are present, the assembly process is basically non-functional.
There are a lot of “theoretical” papers on rejuvenating elastin but there is no way to do that regardless of the amount of tropoelastin in the system. Elastin can be protects and superficial improvements made in the skin but nothing of significance.
Epitalon is a waste of money IMHO and I’ve become skeptical of MOTS-c after doing a “12mg per day for 30 days” experiment with zero results. Yes, 360mg worth. That is the mouse dose that all the internet hype (extremely low dose) is based on when converted to a human that weights 64kg
The attached document says you are wrong and that elastin can be rejuvenated. Moreover, if angiogenesis exists, a new blood vessel is created, and that blood vessel would contain elastin. Therefore the process does exist at least for repair. But normally the loxl and tropoelastin are expressed during gestation and earlier years, yes, I understand that.
The document mentions traditional uses of all-trans retinoic acid (ATRA) aka. tretinoin. If this is used systemically, then you should increase tropoelastin, as well as fbn and I think loxl genes.
Another interesting compound (protein?) found in aqueous dill seed extracts has been shown to modify aged aortas in mice. This is important because it shows that you can alter the aorta, something that is difficult to modify.
So beyond this, the impossible regression of aortic diameter, does actually occur, just as spontaneous repair of dissections (!) This is my interest in the matter.
Epitalon has had clinical trials recently. It did show telomeric repeats were extended. Why is this relevant? Possibly because of the Hayflick limit, which is also increased after exposure to epitalon. This could help with senescence, although idk.
The other reason for my interest in the senolytics is to clear senescent cells from my aorta. I do want to see your regime, I’m considering Fisetin and Quercetin ~1.5 g of each for 3 days or so (?) because I am scared to use FOXO4-DRI. If I clear too many senescent, yet structural cells, I could thin my aorta too much = rupture or dissection. It has been shown that senescent cells accumulate in dilated aortic tissue, and this has a snowball effect increasing inflammatory markers and MMP2 and MMP9 expression.
So yea, increase the telomeric repeats, you shouldn’t feel anything, I wouldn’t imagine, but it should help prepare cells for upcoming division. That’s the safest of the bunch. Senolytics is the scariest, followed by tretinoin, which I don’t think many people would try that out, but from what we know about the compound, it should push ECM into replenish mode while downregulating MMP2 and MMP9 activity.
Why did you like SS31? I’m kinda thinking its raising my BP; my diastolic has been creeping up since I started it last week. MOTS-C idk either, I haven’t tried it. Some people were saying it was a total energy blitz, which I don’t want.
Finally, a fellow traveler! I’ve been taking Life Extension’s Senolytic Activator, combined with some additions to the formula based on my own research into various papers.
However, my experience has been quite poor. I feel like it might be killing off a significant number of healthy cells because I’ve felt extremely fatigued after taking it. I even noticed a few grey hairs appearing—something I’ve never dealt with before—and interestingly, they completely disappeared once I stopped the regimen.
I’m not sure if this is related to my younger age, but I strongly urge the younger members of this forum to be cautious with senolytics. I plan to dive back into the literature to analyze why this might be happening.
One possible reason might be the excessively high frequency of use. You’ve likely heard of PCC1—one of the most potent senolytic (senescent cell clearing) compounds discovered to date.
When I reached out to the author of the research paper, he mentioned that clearing senescent cells generally only needs to be done once every 6 to 8 months; it shouldn’t be done too frequently. However, I recall the Life Extension supplement instructions suggesting once a week. I can’t help but wonder if this is a tactic to encourage more frequent use and boost their profits.
I think weekly is too often as well, but perhaps not if you stick with the very low dose Life Extension sells and you don’t attempt to augment it as I have. Life Extension is structured as a for-profit entity but in the 20 plus years of dealing with them I have found them conservative in setting doses. Their foundation funds life extension research in various forms. The company is pretty responsive to email inquiries from customers but the depth varies, depending on whether they pass the question on to their scientific staff. Send them an email, pointing to the research and see what kind of response you get.
Their formulation contains fisetin and theaflavins as well, though it’s a specific form rather than standard fisetin, which suffers from poor bioavailability. I also deviated from their recommended weekly dosage; based on my review of human clinical trials, I established my own frequency and dosing schedule. Despite that, I still encountered problems. I’ve since stopped using fisetin in favor of other senolytic agents. I might share the details of my research when time permits.
I don’t usually consult these supplement companies because I know they’re just staffed by basic customer service reps. Instead, I go straight to the researchers behind the papers and look at human clinical trials to find the answers.
