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Monitoring Senescent Cell Clearance with Cytokine Levels
Many of us have been attempting to clear our senescent cells with large senolytic doses of Fisetin and/or Dasatinib plus Quercetin. There have been many anecdotal reports of "feeling better" or "more energy" or "reduced arthritic pain" following such treatments, but there is always the worry that we are seeing the placebo effect in action. Some of us have attempted to monitor the results using "blood age" algorithms, but the results have been mixed and rather inconclusive. What is needed is a semi-quantitative way of determining whether and to what degree our senescent cells are actually being cleared.
SASP (Senescence-Associated Secretory Phenotype) is the acronym for the negative effects of the bad molecules released into local organs and into the bloodstream by senescent cells. I found a review entitled "SASPects of Radiation Induced Senescence" and a paper entitled "Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor", both of which give lists of these SASP-related bad molecules. The two most prominent bad actors on these lists are the cytokine molecules Interleukin-6 (IL-6) and Interleukin-8 (IL-8). Therefore, monitoring the concentrations of these cytokines in the bloodstream should be a good way of monitoring whether and to what degree senescent cells are being cleared by senolytic treatments.
I note that LifeExtension offers an Interleukin-6 (IL-6) test for $75, an Interleukin-8 (IL-8) test for $199, and a Cytokine Panel test that includes Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor necrosis factor alpha (TNF-α) for $399. It seems to me that it would be an excellent idea to do at least the IL-6 test (and perhaps the more expensive ones) before and after taking large senolytic doses of Fisetin and/or Dasatinib plus Quercetin. I wish I had done this before my recent senolytic adventures.
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I saw today that Unity is adding 24 people to it's phase 1 trial because of the apparent positive results in clinical 1 trials of UBX0101
" This expansion is intended to provide supplemental data for the trial, allowing the company’s researchers to analyze the fluid in the knee joints of patients in order to measure the harmful chemicals (known as the SASP) secreted by senescent cells. Low SASP levels in this fluid suggest that the drug was effective in destroying these harmful cells and may be more likely to be successful in future trials."
I hope to find something long before they will get through FDA but at least it's good that multiple companies are working on the issue.
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Hi JGC
Thank you for the information. I was in no way promoting Unity if that is how it came off. I watch pretty much anything related to Aging and therefore I see Aubrery De Grey and Mr Faloon talk about the various studies that are taking place and then make a note of it whenever I see anything new.
Has there been any animal tests with Fisetin? I am skeptical of that working because I would have thought anything naturally occurring would have been discovered if it had a big impact on the zombie cells. However it is cheap and worth a try.
I was wondering if you might know anything about the Rapamycin info that is here. I tried using the "research" code but it is not working.
I really appreciate the information you have provided.
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Thank you again for your time.
Rapamycin is a wild card for sure. I have watched every video on it that I could find and the proponents such as Peter Attia and Matt Kaeberlain say that Rapamycin is the only thing that has universally extended life in all animal models , yeast etc. When mentioning the immune system , there seems to be no measurable instances of mortality from animals dying as a result of diseases that one would expect if our systems were weaker. I should go back and refresh but I believe it had to do with the very limited amounts one would take vs larger amounts in transplant patients. That said , Doctor Attia of course pointed out that it is not approved and he would not advise anyone until we know more.
When I was looking for a source , I did find a forum with people taking it , and a very positive write up by a Canadian doctor who had used it for two years. He did make sure to point out that it was his experience and that he was in no way promoting people taking it.
There was an approved study on a small group of seniors , some of which were in middle stages of alezhemirs . One senior that was around 90 had regained his faculty's and was back doing lawn care etc. The study was mainly for safety , but there was suppose to be follow ups. The family was very upset that at the end of three months , their father was no longer able to get any ( as the study ended) and soon he reverted back to the foggy state he had been in at the start.
JGC I am on the same page with the Rapamycin especially when my mom is 86. However one thing that has been consistent in the studies is that Rapamycin appears to reverse some aspects of heart disease and the last study found a 25% increase in refraction ( I think that's the word) allowing more oxygen to the blood stream as the heart was much less strained.
IF anyone is interested and we decide to ease in to it , I will people know how things progress or any issues causing us to stop. I see a source for dasitinab and will try the Fisetin before a decision on Rapamycin. My mom still looks after herself well and I would just like to see her have more energy etc.
Thanks Again
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JGC said:
I note that LifeExtension offers an Interleukin-6 (IL-6) test for $75, an Interleukin-8 (IL-8) test for $199, and a Cytokine Panel test that includes Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor necrosis factor alpha (TNF-α) for $399. It seems to me that it would be an excellent idea to do at least the IL-6 test (and perhaps the more expensive ones) before and after taking large senolytic doses of Fisetin and/or Dasatinib plus Quercetin. I wish I had done this before my recent senolytic adventures.Fully agree. Your post convinced me to add to a recently inflammatory panel both the IL-6 and TNF-alpha as baseline.
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JGC said:
I note that LifeExtension offers an Interleukin-6 (IL-6) test for $75, an Interleukin-8 (IL-8) test for $199, and a Cytokine Panel test that includes Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Interleukin-8 (IL-8), and Tumor necrosis factor alpha (TNF-α) for $399. It seems to me that it would be an excellent idea to do at least the IL-6 test (and perhaps the more expensive ones) before and after taking large senolytic doses of Fisetin and/or Dasatinib plus Quercetin. I wish I had done this before my recent senolytic adventures.Quite happy of my last inflammation panel results which included: hr-CRP, ferritin, leucocytes, fibrinogen, ESR, IL-6 and TNF-alpha.
IL-6 tested at < 1.5 pg/ml (ref. < 7.0) and TNF-alpha at < 4.0 pg/ml (ref. < 8.1). Any data from your side?
Specifically for senolytics we should look maybe more at matrix metalloproteinase Mmp12 vs. IL-6 and p16Ink4a. But that is a bit far from the clinic. Please refer to Aubrey de Grey book (Ending Aging, Chapter 10) and also this paper (at least for mice):
"...Nevertheless, the matrix metalloproteinase Mmp12 represents a robust SASP factor that showed consistent age-dependent increases in expression across all tissues analyzed in this study..."
"... In this study, we did not observe significant age-dependent upregulation of the prominent SASP cytokine Il6 in any tissue, although an upward trend was observed that was consistent in magnitude with previous observations in the heart and kidney (Baker et al., 2016). This modest agerelated upward trend could be explained by a previous report which demonstrated that senescent cell-secreted IL-6 acts in an autocrine manner, reinforcing the senescent state, rather than inducing senescence or promoting dysfunction in neighboring cells (Kuilman et al., 2008)..."
"...Thus, utilizing p16Ink4a-expressing cells as a biomarker of tissue aging and a target of senolytic therapies could prove to be an effective strategy in the future treatment of age-related diseases in humans..."
Hudgins AD, Tazearslan C, Tare A, Zhu Y, Huffman D, Suh Y. Age- and Tissue-Specific Expression of Senescence Biomarkers in Mice. Front Genet. 2018;9:59.