Senolysis – how to do it

Article content: (A) Senolytics should be taken with a small, fatty meal. (B) Senolyse can also be done with supplements alone, not as effectively, but still effective.

Prologue – I need another Senolyse. Every two years, my vision begins to deteriorate, and I’m now longing for computer glasses again. If this happens, I now know:

It’s time to reduce the senescent cells that have recently accumulated due to age.

the link to this post goes via google translator and gives you the english version

After Senolysis: Stem Cell Stimulation

As described in the article linked above, I perform stem cell stimulation with Filgrastim after senolysis. In practice, 2 x 30 million IU of the drug are sufficient. Unfortunately, this is relatively expensive, so the entire senolysis treatment costs me €600 (purchase price), but the results are worth it to me.

I have already undergone senolysis twice: in 2021 and 2023, and each time there was an improvement in the age-related complaints that had accumulated up to that point.

• Most impressive was always the improvement in reading on the computer, sharp vision,
• my heart (also due to the mRNA vaccination) and
• my appearance – many compliments along the lines of: Doctor, you look so much younger……
• the age of my blood vessels has improved by about 15 years.

Performing Senolysis

I follow the standard procedure with quercetin+fisetin+dasatinib, while many of my colleagues only use the dietary supplements quercetin+fisetin and then possibly add spermidine.

The AI gives the OK for this (see below), but for myself, I’ll stick with the officially researched variant with the chemotherapy drug dasatinib, as there are many studies on this, and we’ve started with them.

Since 2021, clinical trials have been on hold

Such a fascinating topic – there should be at least 120,000 entries on Scholar by now, it remains at 12,000, just like in 2021. That’s absolutely striking!

The study landscape has completely collapsed, and just like the miraculous stem cell inducers from Biosplice, which have not progressed in the last 5 years in clinical trials, I would argue, that this fantastic regenerative medicine is agenda-contrary and is therefore hindered and we “normal people” will never officially receive this.

Senolysis is particularly important after any cancer therapy

because chemotherapy and radiation alone induce senescent cells, which influence the patient’s overall life course. That’s why there’s a lot of research evidence that after chemotherapy and radiation, senolysis must be performed ONCE to also wipe out the senescent zombie tumor cells!

By the way… I was extremely early…

I have to say that I first researched and reported on Senolyse very early on – in 2018, in fact.

The dosage method may be important

But since we’re looking for Dr. Since Dr. William Makis also treats tumors with ivermectin and learned that bioavailability increases 2.6-fold when taken with fat, I asked about the senolytics.

How do you take senolysis optimally?

Question for GPT: I treat patients with senolysis with quercetin, fisetin, and dasatinib in my office. My question to you is: is it better to take the medication with food or fat, or on an empty stomach?

Answer: The bioavailability and efficacy of quercetin, fisetin, and dasatinib as part of senolysis therapy can be influenced by the time of administration and the accompanying substances (e.g., fat, food). The scientific data on this vary depending on the substance. Here is a well-founded summary:

Quercetin

• Lipophilic, low bioavailability
• Bioavailability is significantly increased when taken with fat
• Studies show higher plasma levels when taken with a fatty meal
• Combination with bromelain, vitamin C, or resveratrol can also increase absorption

Recommendation: Take with fatty food (e.g., avocado, nuts, oils)

Fisetin

• Also lipophilic, very Low oral bioavailability
• Animal studies and pharmacokinetic data show: Fat intake increases absorption
• Nanoformulations or liposomal variants significantly more effective, but expensive
• Combination with fat or piperine (black pepper) could help

Recommendation: Take with fatty food (possibly additionally piperine or liposomal form)

Dasatinib

• Hydrophilic substance, approved as a chemotherapeutic agent
• Bioavailability is not significantly influenced by fat
• Manufacturer’s information (Sprycel®): Take without regard to meals, but ideally not on an empty stomach due to potential gastrointestinal Side effects
• CYP3A4 metabolism: Avoid interactions with grapefruit, St. John’s wort, etc.

Recommendation: Take not on an empty stomach, but not necessarily with fat – a small meal is sufficient

Summary

Conclusion:
For optimal senolytic effect, always give quercetin and fisetin with a high-fat meal (e.g., olive oil, avocado, nuts).

Take dasatinib with a small meal to minimize side effects – fat is not necessary here.

Senolysis only with biological substances

Question: Colleagues of mine (e.g., Dr. Surböck in Mariazell) are conducting senolysis with quercetin + fisetin + spermidine. Is there a rationale for this? Aren’t all the studies conducted with dasatinib?

Answer: Yes, there is a rationale for the combination of quercetin + fisetin + spermidine for senolysis, even though the classic senolytic studies were originally mostly conducted with dasatinib + quercetin (D+Q). Here is a structured overview of the scientific basis and classification of the alternatives:

Dasatinib + Quercetin (D+Q)

• Gold standard of preclinical research
• Synergistic effect:
  • Dasatinib (a tyrosine kinase inhibitor, originally an oncology drug) acts selectively on senescent preadipocytic cells
  • Quercetin (a flavonoid) has a stronger effect on endothelial and fibroblastic senescent cells
• Demonstrated in animal models:
  • Removal of senescent cells
  • Improvement of signs of aging, vascular function, pulmonary fibrosis, osteoporosis Insulin resistance
• Few human studies, mostly Phase I or II with small groups (e.g., idiopathic pulmonary fibrosis, diabetes, CKD)

Fisetin (alone or with quercetin)

• Fisetin (similar in structure to quercetin, from strawberries, apples, etc.) also has a senolytic effect, sometimes more potent than quercetin
• Studies:
  • Yousefzadeh et al., 2018 (EBioMedicine): Fisetin extended lifespan and reduced senescence markers in mice
  • Showed fewer side effects, potentially broader cell targeting
• Advantage: Dietary supplement, no prescription required like dasatinibCombination of fisetin + quercetin = possible additive effect, but no large comparative studies to date

Spermidine

• Not a classic senolytic, but a senomorphic or autophagy-stimulating moleculeEffect:
  • Activates autophagy, reduces inflammaging, improves mitochondrial function
  • Can slow down senescence, but does not directly kill senescent cells
• Studies:
  • Madeo et al., Nature Medicine 2016: Spermidine extends life in animal models
  • Some small human studies show improved cognitive performance in the elderly

Summary of the rationale

The combination quercetin + fisetin + spermidine is based on the following consideration:

• Fisetin as an effective, well-tolerated senolytic
• Quercetin as a complementary flavonoid partner targeting other cell types
• Spermidine as a companion substance to improve cell clearance and reduce the inflammatory SASP (senescence-associated secretory phenotype)
• Advantage: natural substances, good availability, low side effect profile

But: Limitations

• Little clinical data on the combination
• Data for dasatinib + quercetin are best studied, but limited by dasatinib (side effects, prescription requirement)
• Optimal dosage, timing, and interval therapy are not yet standardized

Conclusion

The combination of quercetin + fisetin + spermidine is based on plausible synergistic mechanisms of action, but hard clinical evidence is currently lacking. In practical application, however, it represents a sensible, low-threshold alternative to dasatinib-based protocols – particularly in a preventive or health-promoting context.