Cell Death Mechanisms Behind D+Q and Fisetin Senolytics
After having done about 9 months of self-experimentation with the effects of D+Q and Fisetin senolytic burst-treatments, I and others in my family have noticed that senolytics with D+Q tends to induce transient flu-like symptoms and a half-day or so feeling of un-wellness, while Fisetin, even taken in 2,000 gram/day doses, does not.
The research on mice indicates that the two senolytic treatments have roughly the same level of senolytic effectiveness. Therefore, I speculate that in the D+Q treatment the immune system is going autophagous, destroying the senescent cells while leaving behind considerable symptom-producing molecular debris, while the Fisetin treatment is triggering aptosis, the natural dismantling of cells that is relatively clean, with little leftover molecular debris.
Comments on this speculation?
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I got plenty of symptoms with 1 gram Fisetin and 1 gram of Quercetin mixed in 1 Tablespoon olive oil with 1/2 teaspoon of ground black pepper, taken on an empty stomach for three day. The symptoms were similar to those of a 4 day water fast, without the gastro-intestinal discomfort. I think the effects on mTOR etc of the combination was similar to that of the water fast.
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Staffan Olsson
I concur with your insights here.
I like 1 gram each of F + C mixed in 1 Tablespoon olive oil with 1/2 teaspoon of freshly ground black pepper, taken immediately. Take on very empty stomach (2 or 3 hours after eating or 1 hour before).
I also like the above with the addition of 1 gram Curcumin. This seemed a bit harsher (more symptoms). I added the Curcumin based on an article I read that indicated it removed senescent cells from intervertebral discs.
I'm about 77 kg and 67 yrs old. I felt quite good both times about a week or so after taking, like you might say about old age related issues, it feels good when it stops...
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Dan Nave
Hi!
I have also felt a distinct vitalizing effect a few days (3-5 days ) after the end of the senolytic treatment, then it fades away. I am 57 years old (in 4 weeks time) and at 74 kg right after waking up in the morning and after urination.
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I forgot to mention in the post above that I took these for three days in a row.
Other considerations (in my opinion):
Take away from other medications.
Stop other supplements for this time.
Reduce your caffeine intake, per Mayo Clinic.
Don’t do any strenuous exercise for a week or two after taking.
Don’t take while sick or healing.
If you are under 45 years old or so you might just want to take this once or twice a year as a prophylactic and not worry too much about symptoms...
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I've just started the fisetin mayo protocol and after day 1, I'm feeling like shit. I took 20mg/kg (1800mg) with MCT oil, spreading the dose out into 3 administration's throughout the day. I woke up this morning feeling terrible. Headache, sore muscles etc. I'm only 41 but suffer from multiple auto-immune conditions so feel that the protocol would benefit me. I'll update after a few weeks as there aren't many folks in my age group sharing their stories of self-experimentation.
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Katy Weston What do do expect? You are supposed to feel terrible
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Andrew P K Yap ???? Both wife ( 75 yo)and I (80 yo) have been following Mayo protocol for a year and neither of us have had anything but positive results. A number of others on this forum also reported only positive effects. You can check the numerous postings in the fisetin topic section.
We take the 20 mg/kg dose on two consecutive days/ month on an empty stomach first thing in the am and do not eat for ~ 4 hours. Every other month I follow the protocol 2X that month.
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Katy Weston Katy see my comment to Mr. Yap's comment on your reaction to fisetin. It "may" be that you had a reaction to the MCT. I tried MCT it several years ago and had an extreme reaction in that I broke out in hives over most of my body. This response to MCT has been noted by other if you check google.
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Katy Weston did you buy low quality 10% fisetin?
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Peter H. Howe MCT oil is something I routinely supplement with and experience no adverse reactions to so I don't think it's that. I'm definitely experiencing an inflammatory reaction, similar to what I would experience when eating gluten or another food I'm sensitive to. Muscle aches, headache, stiff neck etc... I used this product: https://ca.iherb.com/pr/california-gold-nutrition-fisetin-with-novusetin-100-mg-180-veggie-capsules/101509?rcode=ABO0110
Perhaps it's not as good quality as I thought.
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Katy Weston Katy, am sorry to hear that as I think fisetin is perhaps a wonder supplement for someone my age. I use Swanson's fisetin and consume 1.5 grams (20mg/kg) on two consecutive days on empty stomach when I first get up. I do not eat for ~ 4 hrs afterward. I note that several on this forum also includes some type of oil or black pepper combination.
Hope it works out for you. Sorry about inflammation and autoimmune disease.
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Katy Weston It seems that this particular senolytic protocol might not be beneficial for you. In a PubMed document it is suggested that increasing autophagy could in fact be harmful for some conditions.
"Alterations of autophagy contribute to the progression of various autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and systemic sclerosis (SSc). In patients with SLE, autophagy defects result in poor clearance of phagocytic fragments and excessive secretion of inflammatory factors. The disorder of autophagy in IBD patients is closely related to the regulation of inflammatory factors and the clearance of pathogenic pathogens of enteropathy. The increase of autophagy in synovioblasts of RA patients will promote RA-associated synovitis. The autophagy of fibroblasts in SSc patients is dysfunctional, leading to overactive wound healing. Understanding the role of autophagy in the pathogenesis may give us hints on the therapy of autoimmune diseases."
I believe it was worth a try, but given your reaction it doesn't seem its is something you should continue with.
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chuck stanley can you tell me the source of this quote? Id like to further explore this connection. I do quite a few protocols to promote autophagy including fasting and always feel amazing while doing them. It's possible that I need to have some sauna sessions to clear out the debris from this senolytic protocol.
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Katy Weston
Here is the document I quoted from: https://pubmed.ncbi.nlm.nih.gov/32671763/
And here is another one of interest: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346336/
Please keep us posted on your experiments and your progress.
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chuck stanley autophagy? That is not what senolytics do. Senolytics trigger apoptosis or cell death in senescent cells not autophagy.
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Katy Weston You took too high of a starting dose. I have autoimmune problems too and small doses like 500mg of fisetin wrecked me. I felt horrible for a couple of days and then I felt better. But I took more rounds with smaller doses and worked my way up to higher doses and can tolerate 1,000mg+ now. You just need to start small, find a dose that you can tolerate and work your way up to mayo clinic doses. I suspect senescent cells are somehow involved or aggravate autoimmune problems, so the good news is you can greatly improve your condition if you purge them, you just have to work your way up to it.
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Fred Cloud Corrected. Important Distinctions.
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Peter H. Howe I'm not saying that it doesn't work over time.
During treatment, you can expect to feel the effects of the treatment. You don't expect to feel great during treatment. It's the price you pay.
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Andrew P K Yap Not "my" and many others experience with fisetin.
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Peter H. Howe
My experience is that during treatment I feel terrible.
After stopping treatment and after the body heals itself, I feel wonderful.
Because I feel wonderful after treatment (after the body heals itself), I continue with the next round of treatment even when I feel awful during treatment.
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Katy Weston The first time I took the protocol I had a much more noticeable reaction than with subsequent doses. If you initially have a high number of senescent cells you might expect that.
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